Without a fully effective vaccine, prophylactic measures, or sufficient treatment options, dengue has emerged as a significant global health threat. The Pacific Islands are particularly susceptible to dengue as they provide favourable conditions for the Aedes mosquito population, the vector responsible for spreading the virus. Strong public health protocols with an emphasis on vector control are considered to be the best way to combat dengue in this region. However, for a variety of social, economic, environmental and political factors, vector surveillance and control mechanisms are failing. This review seeks to provide an overview on the emergence of dengue in the Pacific Islands, why this region is susceptible due to virus and vector factors, and what has been done and can be done in the future to contain the dengue threat in this region.
Dengue virus is a vector-borne disease primarily spread by the Aedes mosquito population; it is one of the most significant infectious diseases that remains without definitive prevention or treatment options. Due to a variety of environmental and social factors, the Pacific Islands are particularly susceptible to dengue and other arbovirus.[1, 2] This has significant associated morbidity, mortality and economic cost, particularly when patients contract ‘severe dengue’.[1-3] A diagnosis of dengue can be based on clinical signs and/or laboratory diagnosis, whilst a diagnosis of ‘severe dengue’ is based on serious complications including plasma leakage, severe haemorrhage or severe organ impairment. These clinical manifestations and complications of dengue can cause severe illness, particularly in susceptible patient groups including children.
Treatment options are limited particularly in resource poor settings, and thus preventing dengue and recognising outbreaks is critical. Dengvaxia, a world-first dengue vaccine, has recently been approved for use in endemic settings, with the World Health Organization recommending high-risk nations implement it as part of their vaccination program.[4-6] However, the vaccine has variable levels of efficacy, and is not yet considered a cost-effective solution.[5, 6] Whilst dengue remains a growing threat, the Pacific Island region must urgently develop alternative cost-effective diagnostic, detection, treatment and prevention strategies.[4, 7, 8]
The intended focus of this literature review was dengue in the Pacific Island region. An Ovid MEDLINE search was conducted combining the search terms “Dengue”, “Aedes” and “Pacific”. Grey literature and data was also sourced from the World Health Organization (WHO) and other non-profit organisations. Additional resources were identified through analysing the articles retrieved through these searches.
Dengue has been reported in several Pacific Island nations since the 1950s, but in the past decade the incidence has grown exponentially.[1, 9] Whilst in 2000 there was only 50 reported cases per 1000 people, by 2012 this had grown to 350 per 1000. It is difficult to determine reliable data on the endemic levels of dengue in the Pacific Islands, as this depends on accurate and timely reporting to the Pacific Public Health Surveillance Network, still under development. However, whilst dengue is not endemic in all Pacific Islands, it is emerging in previously untouched islands including the Solomon Islands and Papua New Guinea. From 2016 to 2017 alone, there has been an unusual increase in dengue illness reported in the Solomon Islands, Vanuatu, Fiji and Palau. With this growth, some reports indicate that the vast majority of the Pacific Island population will be infected at some point in their lives. In Samoa, one study showed 96% of the population tested positive for IgG antibodies, indicating prior infection. With 89% of 18-25 year olds testing positive, this demonstrated that most Samoans first contracted dengue during childhood, when dengue illness is more likely to be fatal.[7, 11]
Dengue typically follows an epidemic pattern with 1 of the 4 serotypes causing outbreaks across the Pacific every three to five years. However, the number of outbreaks of concurrent serotypes has been growing. After an outbreak of a single serotype, this strain of the virus tends to circulate throughout the region until the next outbreak of a different strain occurs. A single outbreak can affect a large portion of the population, with the 2009 outbreaks affecting 14 Pacific nations. During such outbreaks, complications increase, placing a burden on hospital resources, with 4% of the Federated States of Micronesia’s population requiring hospitalisation during the Kosrae state outbreak. The frequency of outbreaks appears to be increasing, though this may be due to improved surveillance.
Dengue virus (DENV) is a single-stranded, positive-sense RNA virus of the Flavivirus genus. There are four serotypes DENV-1 to DENV-4. Though they only share 65% of their genomes, their clinical syndromes are nearly identical, and they all occupy the same ecological niche.[16, 17] Dengue epidemics usually result from introduction of a single serotype from hyper-endemic countries, which will remain dominant in the region for several years.[12,18,19] However, in 2012, outbreaks of all four DENV serotypes were noted in a single year . Each DENV serotype has caused outbreaks or been prevalent in the Pacific Islands at various times (Table 1).
Table 1: Dengue Serotypes and Epidemiology
|DENV Serotype||Notable related epidemiology and outbreaks|
|DENV-1||The most prominent serotype in 2012-2013, causing the largest-ever documented outbreak affecting New Caledonia.|
|DENV-2||Caused recent outbreaks in Tuvalu and a current outbreak in Samoa.[10, 22]|
|DENV-3||After 18 years of absence, has recently become the dominant serotype in the Pacific islands causing five ongoing outbreaks .|
|DENV-4||Caused one outbreak since 2012, is rare in the Pacific Islands .|
Repeated infection of DENV of the same serotype is associated with increase risk of progressing to severe dengue, which is associated with higher morbidity and mortality if left untreated. Those living in endemic areas such as the Pacific Islands are at an increased risk of being reinfected and thus complications are more common.
Dengue, zika, chikungunya and other arboviruses are transmitted to humans through the bites of infected Aedes mosquitoes. Aedes aegypti is the primary vector in the Pacific Islands and is widespread across the region except for Futuna and other isolated islands.[26,27] Aedes aegypti is associated with human migration and urbanisation, enabling it to be dominant in the region, however, Aedes albopictus, Aedes polynesiensis and nine other potential vectors have also been identified in the Pacific Islands.[27, 28]
Aedes mosquitoes begin their transmission cycle upon acquiring the dengue virus from the blood of a viraemic person; the virus then replicates in mosquito midgut epithelium before shedding its progeny into the haemocoel, which then disseminates into secondary target tissues such as salivary glands. During the next feeding event, the mosquito transmits the virus to the host through saliva.[29,30] Aedes aegypti is capable of repeatedly transmitting the virus through this process irrespective of its number of hosts.
The introduction of Aedes aegypti into different islands has been spurred by human migration; there have been intense population migrations in the Pacific Islands since European colonization. Though the first dengue epidemic in the Pacific Islands was reported in the 1880s, descriptions of Aedes aegypti didn’t emerge until the 1960s in Fiji and Tonga.[20, 32, 33] Aedes aegypti then spread during World War II, when travel between the Pacific Islands and Asia, Europe, and America became more frequent. Recent studies have now identified genetic variability in nine locations across Fiji, New Caledonia, Tonga and French Polynesia, suggesting a link between human migration and Aedes aegypti populations, possibly related to island isolation and environmental conditions.
Several factors influence the transmission of DENV from mosquitoes to humans, including climate. Higher temperatures enable the virus to replicate in higher concentrations, enhancing the vectors’ risk for pathogen transmission and contributing to the high prevalence of dengue infection in the tropical Pacific Islands Globally, climate-induced variations in modelled Aedes aegypti populations were strongly correlated to historical dengue cases between 1958 to 1995. Recent research from New Caledonia, where dengue spread by Aedes aegypti is a major public health problem, showed that the epidemic dynamics of dengue were predominantly driven by climate in the last forty years. Another study found a positive correlation between dengue infection and El Nino southern oscillation in ten countries, with evidence of infection spreading from larger islands to smaller surrounding islands. It is predicted that global warming will increase the latitudinal and altitudinal distribution of Aedes aegypti and subsequently DENV.[38,39]
Dengue Surveillance Methods
Dengue surveillance and tracking is essential to enable timely epidemic responses. Though representatives from the Pacific Islands believe there is adequate surveillance infrastructure and systems, governments have not emphasised prevention. These systems must be strengthened to more accurately track dengue epidemiological data [8, 40]. Given financial difficulties, this may be better accomplished through alternative mechanisms.
One such alternative is the transport of serum and blood samples internationally. When a new serotype emerges in one Pacific country, this is often followed by outbreaks in neighbouring countries ; using blood samples to identify emerging serotypes enables surveillance of viral spread across the region. Filter paper (FP)-dried blood spots have minimal health risk and so are not bound by dangerous goods regulations present in several Pacific nations . Blood spiked with cultured DENV can be blotted on FP-cards and the serotype determined using reverse-transcriptase polymerase chain reaction.. The serotype and genotype of DENV can be identified using FP-dried serum even after being transported over thousands of kilometres at tropical temperatures. This method of surveillance particularly useful in the Pacific Islands, where samples may need to be transported over long distances.
Another method to monitor dengue levels is the use of international travellers as ‘sentinels’, so that the risk of dengue infection can be estimated through proxies who travelled to particular areas. Patterns of local dengue incidence in the Pacific Islands were shown to be closely correlated with patterns of dengue incidence imported from the Pacific to New Zealand. However, this method is more commonly retrospective and cannot provide an indication of outbreaks. A combination of both methods could be implemented to cheaply and effectively improve dengue surveillance in the regions.
Dengue Prevention and Control, Now and in the Future
Strategies and Policies
Many nations have been attempting to meet the WHO infectious disease strategy objectives (Figure 1) by implementing policies that address vector surveillance, health education for vector control and dengue prevention, and emergency response capacity. However, an urgent policy review to combat dengue is needed, with a focus on emphasising dengue in climate change and environmental medicine policies. It is also essential that dengue is classed as a notifiable disease across all Pacific Islands through legislation.
A Dengue Vaccine
Although several live-attenuated dengue vaccines are undergoing phase III clinical trials, currently Dengvaxia (CYD-TDV) is the only vaccine that is licensed and registered for use in individuals aged 9-45 years and living in dengue endemic areas. Modelling has shown that Dengvaxia would only have the highest net benefit and be most cost-effective if the majority of the population is vaccinated in dengue-endemic nations. The WHO has recommended that nations with a high burden of disease, defined as seroprevalence >70% in 9 year-olds, introduce the vaccine.[4, 1] However, many nations worldwide are still debating this, and Dengvaxia is not currently licensed for use in Pacific Island nations.[5, 51]
From the two major phase III clinical trials for Dengvaxia, overall vaccine efficacy against severe dengue was 79%, however, this varied by serotype, age at vaccination, and previous dengue infection. For those with a previous dengue infection, vaccination efficacy was 78%, however, it was only 38% for those with no prior infection. In fact, a study has shown that Dengvaxia can also increase the risk of hospitalisation when seronegative individuals are vaccinated and later experience natural secondary dengue infection. The pooled efficacy for those older than 9 years old was higher than those under 9 years of age, who have a higher risk of severe dengue (66% vs 44%).[3, 52] Finally, in terms of serotype, vaccine efficacy was shown to be higher against serotypes 3 (72%) and 4 (77%) than for serotypes 1 (55%) and 2 (43%).
Further study is ongoing to determine whether dengue illness and hospitalisation has reduced in nations that have implemented Dengvaxia.[53, 54] However, with varying efficacy, and questions regarding long-term safety and cost-effectiveness, it is predicted that vaccination will only be possible in the Pacific Islands if it is priced competitively.[53, 54] Thus, for the time being, vector control will remain the focus of dengue control strategy in the Pacific Islands, with the aim of integrating vaccination once it is more efficacious and cost-effective. At present, it is far more affordable and effective to combat dengue by improving vector control mechanisms, and vaccination will be most useful as an adjunct if appropriate for specific nations.
Vector Control: Currently Used Methods
Vector control currently offers the best option for preventing dengue, but delivery of prevention programmes in the Pacific Islands is often inefficient, ineffective or both. Several mechanisms exist in various Pacific Islands to control outbreaks once they occur, however some of the most common efforts, such as pesticide spraying, have limited effectiveness.
Factors that increase the risk of dengue transmission have included poor household drainage and hygiene problems, issues that can be addressed by health education programs to build a ‘prevention attitude’ among Pacific residents.[57, 58] However, it is believed that improving health education, awareness campaigns and technical support is necessary to ensure successful vector control. Environmental factors such as buckets of stagnant water, allowing mosquitoes to breed, and host larvae and pupae, are other key risk factor which could be targeted through education campaigns. Chemical treatment of breeding sites, insecticide spraying and biological control by introducing predators are mechanisms already utilised by some Pacific Islands which could be further implemented for vector control in the future.
Vector Control: Innovative Approaches
Novel vector-based approaches aimed at controlling dengue include the use of obligate intracellular bacterium Wolbachia pipientis, which interferes with reproduction in over 40% of insect species. Although Wolbachia does not occur naturally in Aedes aegypti species, transinfection has been shown to be successful. Recent studies in Cairns, Australia have shown stable transinfection of natural A. aegypti populations with the wMel strain of Wolbachia, rising to near-fixation within a matter of months and remaining established in those field sites unaided. The antiviral activity of wMel has shown to be highly effective in laboratory studies even one year after field release. The evidence supports the long-term stability of Wolbachia against the dengue virus, however, the effects on reduction of human disease in dengue-endemic regions is yet to be established, this is currently under investigation in Indonesia and Vietnam.
Another promising vector control method is the sterile insect technique (SIT), which has historically been successful against a multitude of agricultural pests. In the 1960s, large-scale SIT programs enabled the elimination of A. aegypti from 23 American countries. SIT has recently re-emerged as a vector control strategy due to innovative technological advances including genetic modification of mosquitoes. Using SIT, Cuba has come close to the eradication of A. aegypti  and Singapore has kept levels of the mosquitoes down for more than 30 years. Though neither of these methods is currently used widely in Pacific Islands, these innovative strategies are potential cost-effective vector reduction methods.
Emergency Response Capacity
There is a significant need to grow emergency-response and outbreak-response to combat dengue. Currently, the WHO and Red Cross manage the majority of outbreak control, both logistically and financially[14, 71] The Pacific Public Health Surveillance Network has provided some support in capacity building, and multiagency response teams have successfully been implemented during some outbreaks, but there remains a need to engage Pacific Directors and Ministers of Health to help prepare these multidisciplinary response teams for future outbreaks.[2, 14]
Dengue remains a significant threat in the Pacific Islands, with prevalence levels and the number of outbreaks continuing to increase. Until Dengvaxia or another dengue vaccine has a proven cost-effective public health benefit beyond the currently calculated values, it is unlikely to be deployed in Pacific Islands.[5, 51] The best hope for containing dengue is by improving region-wide surveillance and cost-effective, sustainable vector control mechanisms [6-8]. This requires Pacific Island governments to integrate dengue prevention into their environmental and public health policy, and work to improve vector surveillance and control methods, which may involve implementing innovative approaches [8, 48]. Another area that requires significant improvement is outbreak response, and upskilling all Pacific doctors to appropriately respond to dengue outbreaks [8, 60]. Ultimately, until the objectives outlined by the WHO are addressed, dengue will remain a growing challenge in the Pacific Islands.[7, 47] These islands must engage with the growing body of organisations working in the region to develop new and innovative surveillance and control approaches and combat dengue in the future.
Madeleine Marsland and Dunya Tomic
Madeleine is a fourth year medical student who is interested in global health and research. She combines these interests in her role as Chief of Editorials and Publications for the Pacific Medical Students’ Association, and is also undertaking research with the Department of Anatomy and Developmental Biology at Monash University. She hopes to pursue global health research and policy.
Dunya is a fourth year medical student at Monash University with a particular interest in clinical research and medical ethics. She hopes to one day combine this with a career as a physician.
Conflicts of interest
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