Sources of Dengue Viruses Imported into Queensland, Australia, 2002–2010

David Warrilow

, Judith A. Northill, and Alyssa T. Pyke

Author affiliations: Queensland Health Forensic and Scientific Services, Archerfield, Queensland, Australia

Abstract

To assess risk for importation of dengue virus (DENV) into Queensland, Australia, and sources of imported viruses, we sequenced the envelope region of DENV isolates from symptomatic patients with a history of travel during 2002–2010. The number of imported dengue cases greatly increased over the surveillance period, some of which were associated with domestic outbreaks. Patients reported traveling to (in order) Asia, Papua New Guinea, Pacific Island countries, and non–Asia-Pacific countries. By using phylogenetic methods, we assigned DENV isolates from returning residents and overseas visitors with viremia to a specific genotypic group. Genotypes circulating in Asia were extremely diverse. Genotyping and molecular clock analysis supported Asian origination of a strain that caused an outbreak of DENV-4 in Pacific Island countries during 2007–2009, and subsequently, in Innisfail, Australia, in 2009. Our findings indicate that Asia is a major source of DENVs that are imported into Australia, causing a risk for epidemics.

Queensland, a state located in the tropical and subtropical northeastern area of Australia, has a long history of dengue virus (DENV) activity. Dengue was present in the late 19th century (1) and, following a lull for most of the 20th century, dengue importation and epidemic transmission have been increasingly reported in the past 20 years (2,3). Epidemics of the disease have occurred historically in other states of Australia, but only in Queensland have epidemics been reported in recent times. These epidemics were caused by the distribution of the vector, Aedes aegypti mosquitoes. The species was once found in other Australian states, but its area of distribution has now contracted so that it lies almost exclusively within Queensland’s borders (4,5).
Despite repeated transmission events, dengue is not endemic to Queensland, and transmission requires a viremic traveler to import the virus to initiate epidemic spread (6). Rapid identification of cases and disease tracking, incorporating targeted vector surveillance, and control measures adopted rigorously to limit epidemic potential have been major factors in preventing local transmission and in reducing the cost of managing mosquito-borne disease (7).
With the apparent increasing frequency of dengue epidemics and imported cases, the disease has become a major public health issue. Exposure to multiple serotypes of DENV, of which there are 4 in total, may result in a higher probability of potentially life-threatening conditions such as dengue hemorrhagic fever and dengue shock syndrome, a potentially life-threatening condition (8). Perhaps not coincidentally, 2 fatal cases of dengue hemorrhagic fever were reported in 2004 in Queensland, and the serologic profile of the case-patients indicated secondary infection consistent with dengue shock syndrome (9). Of additional concern is the possibility that the virus may become endemic if case numbers were to rise to a point at which vector control measures became ineffectual at controlling virus spread.
Recent DENV infection is diagnosed by serologic testing, through virus isolation or by nucleic acid amplification by reverse transcription PCR (RT-PCR). The advantage of the latter is that sequencing of reaction products enables a definitive diagnosis of acute infection, identification of the virus serotype, and genotyping. As an adjunct to isolation techniques, sequencing and genotyping can provide valuable evidence of importation or can confirm local transmission and enable differentiation between multiple circulating strains and serotypes. Analysis of DENV sequence data facilitates rapid disease tracking and vector control. However, not all specimens are suitable for RT-PCR because infected persons usually exhibit a relatively short-lived viremia early in the febrile period (10). In addition, clinicians may find it difficult to obtain acute-phase samples, particularly if patients delay their initial consultation or are still in transit during their viremic phase.
As part of control measures by Queensland Public Health, we sequenced the envelope region of DENV isolates from symptomatic patients with a history of travel during 2002–2010. The proportion of the 4 DENV serotypes that were imported was determined, as well as the geographic origin of each serotype. Phylogenetic trees containing imported DENV viruses and others strains circulating throughout the world (from GenBank) were constructed by using a maximum likelihood model. From this analysis, we ascertained the likely geographic origin of imported viruses. This enabled us to assess the risk for importation of DENV from various sources by travelers entering Australia.