Confronting the emerging threat to public health in northern Australia of neglected Indigenous arboviruses

In excess of 75 arboviruses have been identified in Australia, some of which are now well established as causative agents of debilitating diseases. These include Ross River virus, Barmah Forest virus, and Murray Valley encephalitis virus, each of which may be detected by both antibody-based recognition and molecular typing. However, for most of the remaining arboviruses that may be associated with pathology in humans, routine tests are not available to diagnose infection. A number of these so-called ‘neglected’ or ‘orphan’ arboviruses that are indigenous to Australia might have been infecting humans at a regular rate for decades. Some of them may be associated with undifferentiated febrile illness—fever, the cause of which is not obvious—for which around half of all cases each year remain undiagnosed. This is of particular relevance to Northern Australia, given the Commonwealth Government’s transformative vision for the midterm future of massive infrastructure investment in this region. An expansion of the industrial and business development of this previously underpopulated region is predicted. This is set to bring into intimate proximity infection-naïve human hosts, native reservoir animals, and vector mosquitoes, thereby creating a perfect storm for increased prevalence of infection with neglected Australian arboviruses. Moreover, the escalating rate and effects of climate change that are increasingly observed in the tropical north of the country are likely to lead to elevated numbers of arbovirus-transmitting mosquitoes. As a commensurate response, continuing assiduous attention to vector monitoring and control is required. In this overall context, improved epidemiological surveillance and diagnostic screening, including establishing novel, rapid pan-viral tests to facilitate early diagnosis and appropriate treatment of febrile primary care patients, should be considered a public health priority. Investment in a rigorous identification program would reduce the possibility of significant outbreaks of these indigenous arboviruses at a time when population growth accelerates in Northern Australia

Diagnosis of Dengue: Strengths and limitations of current techniques and prospects for future improvements

Dengue is an increasingly common mosquito-borne, flaviviral disease of significant public health concern. The disease is endemic throughout tropical and subtropical regions, placing almost half of the world’s population at risk, and each year approaching 100 million people in around 130 countries are infected. There is acknowledged to be four antigenically distinct serotypes of the virus, and arguably a fifth, each of which elicits a full spectrum of clinical disease. This ranges from asymptomatic self-limiting infection to life-threatening severe manifestations characterized by plasma leakage, bleeding, and/or organ failure. Recovery from primary infection by one serotype provides lifelong immunity against reinfection by that particular serotype, whereas with subsequent infections by other serotypes, the risk of developing severe dengue is increased. Rising mortality and morbidity rates caused by infection in recent years are attributable partly to a lack of availability of effective antiviral therapies and vaccines. In this context, early detection of infection with sensitive and specific laboratory tools and the prompt clinical management of this disease is a health care priority. Although a variety of techniques are currently used for laboratory diagnosis of dengue, no single methodology satisfies the ideal requirement for both sensitivity and specificity, while also being rapid and inexpensive. Newer detection tools that can fill this acknowledged gap in dengue diagnosis are urgently required

Vaccine development against dengue, a viral disease of increasing significance to global public health : editorial

Dengue is a mosquito-borne viral disease of humans that is a major public health concern in tropical and sub-tropical regions of the world. The increasing mortality and morbidity rates caused by infection in recent years are attributable partly to a lack of availability of effective antiviral therapies and vaccines. In a concerted attempt to arrest this global expansion, several dengue vaccine candidates have progressed from pre-clinical testing into clinical trials. However, the advancement of vaccine development has manifest challenges to be overcome. A principal tenet underpinning dengue vaccine design is balanced immunity to all five recognised virus serotypes, but difficulties in achieving optimal attenuation of each virus and interference between individual attenuated viruses are significant hurdles to successful implementation. Currently, the most advanced vaccine candidate, the recombinant, live-attenuated ChimeriVax-DEN1-4 preparation developed by Sanofi Pasteur, is likely to achieve licensure at the completion of phase III trials and undergo population safety surveillance. Subunit and DNA vaccines are also in various stages of clinical evaluation. The intrinsic rationale is to produce a safe, efficacious and cost-effective vaccine. While this remains an achievable goal, progress is limited by an incomplete understanding of dengue viral pathogenesis, together with a lack of suitable animal models for fundamental pre-clinical development. This editorial highlights current approaches and future directions for vaccine strategies to combat the global expansion of this infectious disease

Predicting Ross River virus infection by analysis of seroprevalence data

Infection with arthropod-borne (arbo)viruses presents a significant and growing public health threat to the resident population of Queensland (QLD), the north-eastern state of Australia. Clinical infection with Ross River virus (RRV) is the most commonly detected, and arguably most debilitating, of Australia’s 75 known indigenous arbovirus species. Development of prediction models to forecast arbovirus epidemics aims to provide accurate and reliable tools that may facilitate planned interventions by local and state authorities to curb disease transmission. Acute immunoglobulin (Ig)M-positive enzyme-linked immunosorbent assay results are often misleading, with interpretation cautioned. As such, this serological testing was recently excluded as a means to confirm cases of arbovirus infection in Australia. The purpose of this study was to investigate the seroepidemiological value of acute IgM-positive results across QLD by correlating with RRV case reports and to develop a mathematical model to predict RRV outbreaks. Blood samples from patients throughout QLD suspected of arboviral infection were tested for RRV, with numbers for various serology results grouped by geographical region. The serology data were compared with case reports for each respective region by multiple regression in order to determine any relationships. RRV IgM-positive results correlated significantly to the number of case reports per region (P 0.05). Hence, these findings failed to validate the potential use of IgM-positive seroprevalence to predict RRV infection with sufficient accuracy for diagnostic purposes. A possible indirect value may exist, however, in analysing pooled seroprevalence data, which may better inform concurrent surveillance measures and thereby enhance the accuracy of RRV outbreak forecasts

Do neglected Australian arboviruses pose a global epidemic threat?

Arboviruses (Arbo: ARthropod BOrne) remain a concern for public health in Australia. They are transmitted between their vertebrate hosts by arthropods (mosquitoes, ticks, sandflies and midges). Although more than 75 arboviruses have been identified in Australia, for most there is no information as to whether they infect or cause disease in people.1 Clinically, the most important Australian arboviruses are Ross River, Barmah Forest, Murray Valley encephalitis and West Nile (Kunjin strain).2 However, several other arboviruses that are indigenous to Australia also infect humans, including notably Kokobera, Stratford, Alfuy and Edge Hill virus.

The epidemiology of dengue infection: Harnessing past experience and current knowledge to support implementation of future control strategies

All rights reserved.Dengue is the most important mosquito-borne viral infection of humans. Although outbreaks of disease which are now recognized as clinically consistent with dengue have been reported for centuries, it was not until half a century ago that laboratory identification of dengue viruses as the etiological agent of febrile illness was achieved. This debilitating and sometimes fatal disease is widely distributed in >125 countries in tropical and subtropical zones of the world. Asia, South America and the Pacific Islands are hyper-epidemic regions while currently there is less prevalence in Europe, North America and Australia. The estimated global incidence ranges between 200 and 400 million clinical cases per year. While some areas of past epidemics are now considered to be under control, recent decades have witnessed an epidemic rise in dengue worldwide. Major factors facilitating expansion include climate change and increase in urbanization and international travel. Concurrently, the non-availability of an efficacious antiviral drug or vaccine and a lack of effective vector control strategies collectively make dengue a serious public health concern. Thus, it is of paramount importance to analyze the history of the spread of infection and to gain a deeper understanding of patterns of transmission in order to anticipate epidemiological trends more accurately, thereby enabling better preparedness for future outbreaks. © 2016, Malaria Research Center

Knowledge, attitude and recommendations for practice regarding dengue among the resident population of Queensland, Australia

Objective:To investigate levels of awareness of dengue among the inhabitants of Queensland (QLD), a dengue-prevalent state in the north east of Australia. Methods: A computer-assisted telephone interviewing survey was conducted in mid 2014. A total of 1 223 randomly selected respondents (≥ 18 years) across QLD completed a structured questionnaire covering all aspects of dengue. Results: 97.55% had heard of dengue and participated further. Among them, 54.70% had travelled overseas (48.11% to dengue-risk countries) in the last five years. A total of 94.47% said transmission is by mosquito bite. In addition, 84.83% knew of current transmission of dengue in QLD, while 80.97% knew the focus is Far North and North QLD. Furthermore, 2.35% and 8.97% had experienced an infection in their life or that of their immediate family/partner, respectively. 85.03% identified correctly at least one means of prevention. A total of 69.72% advised to use insect repellent, wear covered clothing and avoid visiting mosquito-prone areas while 20.93% advised fumigation and clearing water containers around residences. There was a significant difference (P 0.05). Conclusions: Although many people throughout QLD have heard of dengue, about 15% appear unaware of local transmission, its symptoms and of methods to reduce risk of infection. A lack of knowledge regarding prevention of mosquito breeding is evident in South East QLD, where dengue is not currently reported. The study suggests that future dengue awareness campaigns should target communities in both endemic and potentially endemic areas throughout Queensland

The global spread of Zika virus: Is public and media concern justified in regions currently unaffected?

Background: Zika virus, an Aedes mosquito-borne flavivirus, is fast becoming a worldwide public health concern following its suspected association with over 4,000 recent cases of microcephaly among newborn infants in Brazil. Discussion: Prior to its emergence in Latin America in 2015-16, Zika was known to exist at a relatively low prevalence in parts of Africa, Asia and the Pacific islands. An extension of its apparent global dispersion may be enabled by climate conditions suitable to support the population growth of A. aegypti and A. albopictus mosquitoes over an expanding geographical range. In addition, increased globalisation continues to pose a risk for the spread of infection. Further, suspicions of alternative modes of virus transmission (sexual and vertical), if proven, provide a platform for outbreaks in mosquito non-endemic regions as well. Since a vaccine or anti-viral therapy is not yet available, current means of disease prevention involve protection from mosquito bites, excluding pregnant females from travelling to Zika-endemic territories, and practicing safe sex in those countries. Importantly, in countries where Zika is reported as endemic, caution is advised in planning to conceive a baby until such time as the apparent association between infection with the virus and microcephaly is either confirmed or refuted. The question arises as to what advice is appropriate to give in more economically developed countries distant to the current epidemic and in which Zika has not yet been reported.Summary:Despite understandable concern among the general public that has been fuelled by the media, in regions where Zika is not present, such as North America, Europe and Australia, at this time any outbreak (initiated by an infected traveler returning from an endemic area) would very probably be contained locally. Since Aedes spp. has very limited spatial dispersal, overlapping high population densities of mosquitoes and humans would be needed to sustain a focus of infection. However, as A. aegypti is distinctly anthropophilic, future control strategies for Zika should be considered in tandem with the continuing threat to human wellbeing that is presented by dengue, yellow fever and Japanese encephalitis, all of which are transmitted by the same vector species

Neglected Australian arboviruses associated with undiagnosed undifferentiated febrile illness

Australia is home to over 75 arthropod-borne viruses, with least 13 associated with human infection. Ross River (RRV), Barmah Forest (BFV), Murray Valley encephalitis (MVEV) and Kunjin (KUNV) viruses commonly cause disease and are diagnosed in pathology laboratories. Following commercial ELISA development to diagnose RRV, in 2016 cases exceeded 9,000. However, other indigenous arboviruses, such as Alfuy (ALFV), Edge Hill (EHV), Kokobera (KOKV), Sindbis (SINV) and Stratford (STRV), are not routinely tested. Little is known of their role in human pathology, undifferentiated febrile illness (UFI) or serious diseases. This study aimed to determine prevalence of infection of humans with these neglected Australian arboviruses and whether any causes UFI. Screening of 1,000 age- and gender-stratified plasma samples from healthy Queensland-resident blood donors for antiviral IgG antibodies by indirect ELISA produced non-specific reactivity so a sub-sample was tested by plaque reduction neutralisation. 492 acute-phase samples from UFI patients in northern Australia were also screened by indirect immunofluorescence for virus-specific IgM antibodies. There was a linear increase in prevalence of neutralising antibodies with annual seroconversion rates ranging from RRV 1.3% to KOKV and STRV 0.05%. Among UFI patient samples 5.2% contained IgM against one or more of: RRV 0.8%; BFV 0.4%; ALF 1.4%; EHV 1.8%; KOKV 1.4%; KUNV 2.4%; MVEV 1.0%; STRV 1.2%. No age-dependent anti-ALFV antibodies prevalence was observed. A small proportion of UFI was attributable to infection; 2 ALFV, 4 EHV, 14 KOKV, 8 KUNV, 8 MVEV and 1 STRV identified cases per 1000 persons tested. These results indicate several neglected Australian arboviruses have been infecting humans for decades and some may be associated with UFI. A program of systematic testing of UFI patients is recommended to examine for recent infection to determine the significance of the burden of the disease that these neglected arboviruses cause

Neglected Australian arboviruses and undifferentiated febrile illness: Addressing public health challenges arising from the ‘Developing Northern Australia’ government policy

The Australian Government is currently promoting the development of Northern Australia, with an associated increase in the local population. Consequent to this is the public health threat posed by heightened human exposure to many previously neglected arboviruses that are indigenous to the region. This initiative to support economic activity in the tropical north of the continent is leading to the accelerated expansion of an infection-naïve human population into hitherto un-encountered ecosystems inhabited by reservoir animals and vectors for these arboviruses. Combined with an apparent rise in the number and impact of dramatic climate events, such as tropical cyclones and floods caused by torrential monsoonal rainfall, this heightens the potential for viral transmission to humans. More than 75 arboviruses have been identified in Australia, some of which are associated with human disease but for which routine tests are not available to diagnose infection. Here, we describe briefly the neglected Australian arboviruses that are most likely to emerge as significant agents of human disease in the coming decades. We also advocate the establishment of a thorough surveillance and diagnostic protocol, including developing new pan-viral rapid tests for primary care use to assist in the early diagnosis and correct treatment of affected patients. We propose that the implementation of these activities will enhance our understanding of the geographical range, prevalence, identification and control of neglected Australian arboviruses. This would minimise and limit the possibility of large-scale outbreaks with these agents as population and economic growth expands further into Australia’s tropical north