MicrobiologyBytes

A number of flaviviruses constitute a significant threat to global health. Dengue virus (DENV) infection causes around 21,000 human deaths annually, and it is estimated that at least 120 countries have endemic DENV transmission, whilst in recent years, West Nile virus (WNV) has become more prominent as a zoonotic agent, particularly in North America where the virus first emerged in 1999 and rapidly spread across the continent. WNV has now emerged in a number of European countries, particularly around the Mediterranean basin, where infections in humans, horses and birds have been reported.

Cross-reactivity of sera raised against one flavivirus recognising another flavivirus has been well documented. One consequence of flavivirus cross-reactivity is the occurrence of false-positive results, yet cross-reactivity can lead to cross-protection. Understanding and manipulating the cross-reactive properties of flaviviruses has the potential to assist the development of effective broad-spectrum human vaccines against WNV and other existing and emerging flaviviruses.

Flavivirus-induced antibody cross-reactivity. J Gen Virol. Sep 7 2011
Dengue viruses (DENV) cause countless human deaths each year, whilst West Nile virus (WNV) has re-emerged as an important human pathogen. There are currently no WNV or DENV vaccines licensed for human use, yet vaccines exist against other flaviviruses. To investigate flavivirus cross-reactivity, sera from a human cohort with a history of vaccination against tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV) and yellow fever virus (YFV) were tested for antibodies by plaque reduction neutralisation test. Neutralisation of Louping ill virus (LIV) occurred, but no significant neutralisation of Murray Valley encephalitis virus (MVEV) was observed. Sera from some individuals vaccinated against TBEV and JEV neutralised WNV, which was enhanced by YFV vaccination in some recipients. Similarly, some individuals neutralised DENV-2, but this was not significantly influenced by YFV vaccination. Antigenic cartography techniques were used to generate a geometric illustration of the neutralisation titres of selected sera against WNV, TBEV, JEV, LIV, YFV and DENV-2. This demonstrated the individual variation in antibody responses. Most sera had detectable titres against LIV and some had titres against WNV and DENV-2. Generally, LIV titres were similar to titres against TBEV, confirming the close antigenic relationship between TBEV and LIV. JEV was also antigenically closer to TBEV than WNV, using these sera. The use of sera from individuals vaccinated against multiple pathogens is unique relative to previous applications of antigenic cartography techniques. It is evident from these data that notable differences exists between amino acid sequence identity and mapped antigenic relationships within the family Flaviviridae.

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Dengue virus infection is a growing public health problem with up to 100 million cases annually, and neither vaccines nor effective therapies are available. To search for the ways of preventing and treating dengue infections we need to better understand their molecular mechanisms. As with many other viruses, dengue virus enters cells by fusion between the viral membrane and the membrane of intracellular vesicles (endosomes). In this paper the authors explore the fusion stage of dengue virus entry in different experimental systems ranging from virus fusion to artificial lipid membranes to fusion inside the cells. While earlier work on dengue virus entry has focused on the virus protein that mediates fusion, they found that effective action of this protein requires specific lipid composition of the membrane the virus fuses to. In effect, this lipid dependence allows virus to control intracellular location of the fusion event and, thus, the place of its RNA release by exploiting cell-controlled differences between lipid compositions of different organelles the virus travels through. The essential role of the interactions between dengue virus and its lipid cofactors during virus entry suggests that these interactions may be targeted in drug design.

Dengue Virus Ensures Its Fusion in Late Endosomes Using Compartment-Specific Lipids. PLoS Pathog 6(10): e1001131. doi:10.1371/journal.ppat.1001131
Many enveloped viruses invade cells via endocytosis and use different environmental factors as triggers for virus-endosome fusion that delivers viral genome into cytosol. Intriguingly, dengue virus (DEN), the most prevalent mosquito-borne virus that infects up to 100 million people each year, fuses only in late endosomes, while activation of DEN protein fusogen glycoprotein E is triggered already at pH characteristic for early endosomes. Are there any cofactors that time DEN fusion to virion entry into late endosomes? Here we show that DEN utilizes bis(monoacylglycero)phosphate, a lipid specific to late endosomes, as a co-factor for its endosomal acidification-dependent fusion machinery. Effective virus fusion to plasma- and intracellular- membranes, as well as to protein-free liposomes, requires the target membrane to contain anionic lipids such as bis(monoacylglycero)phosphate and phosphatidylserine. Anionic lipids act downstream of low-pH-dependent fusion stages and promote the advance from the earliest hemifusion intermediates to the fusion pore opening. To reach anionic lipid-enriched late endosomes, DEN travels through acidified early endosomes, but we found that low pH-dependent loss of fusogenic properties of DEN is relatively slow in the presence of anionic lipid-free target membranes. We propose that anionic lipid-dependence of DEN fusion machinery protects it against premature irreversible restructuring and inactivation and ensures viral fusion in late endosomes, where the virus encounters anionic lipids for the first time during entry. Currently there are neither vaccines nor effective therapies for DEN, and the essential role of the newly identified DEN-bis(monoacylglycero)phosphate interactions in viral genome escape from the endosome suggests a novel target for drug design.

Related:

• Dengue Virus
• Pathogenesis and treatment of dengue fever

The incidence and geographic range of dengue and dengue hemorrhagic fever has increased dramatically in recent decades. With 2.5 billion people now living in areas at risk for epidemic transmission, dengue has become the most important mosquito-borne viral disease affecting humans. Dengue virus (DENV) is a positive-strand RNA virus of the family Flaviviridae. It exists as four closely related but antigenically distinct serotypes, all of which have Aedes aegypti mosquitoes as their primary vector, with A. albopictus as a secondary vector.

Mosquitoes, like all insects, are exposed to a variety of microbes in their natural habitats, and possess an innate immune system that is capable of mounting a potent response against microbial challenge. The insect innate immune response is largely regulated by three main immune signaling pathways: the Toll, immune deficiency (IMD) and Janus kinase signal transducer and activator of transcription (JAK-STAT) pathways. The Toll pathway is involved in defense against fungi, Gram-positive bacteria, and viruses, and has been found to be specifically involved in the A. aegypti anti-DENV response.

In order to study the interaction of DENV with the A. aegypti immune response, researchers have characterized the DENV infection-responsive transcriptome of the immune-competent A. aegypti cell line. As in mosquitoes, DENV infection transcriptionally activated the cell line Toll pathway and a variety of cellular physiological systems. Most notably, however, DENV infection down-regulated the expression levels of numerous immune signaling molecules and antimicrobial peptides (AMPs). Functional assays showed that transcriptional induction of AMPs from the Toll and IMD pathways in response to bacterial challenge is impaired in DENV-infected cells. In addition, Escherichia coli, a Gram-negative bacteria species, grew better when co-cultured with DENV-infected cells than with uninfected cells, suggesting a decreased production of AMPs from the IMD pathway in virus-infected cells. Pre-stimulation of the cell line with Gram-positive bacteria prior to DENV infection had no effect on DENV titers, while pre-stimulation with Gram-negative bacteria resulted in an increase in DENV titers. These results indicate that DENV is capable of actively suppressing immune responses in the cells it infects, a phenomenon that may have important consequences for virus transmission and insect physiology.

Dengue Virus Inhibits Immune Responses in Aedes aegypti Cells. 2010 PLoS ONE 5(5): e10678. doi:10.1371/journal.pone.0010678

Related:

• The dengue vector Aedes aegypti
• Dengue Virus
• Rethinking dengue hemorrhagic fever

Aedes aegypti is the urban vector of dengue viruses worldwide. While climate influences the geographical distribution of this mosquito species, other factors also determine the suitability of the physical environment for this mosquito. Importantly, the close association of Ae. aegypti with humans and the domestic environment allows this species to persist in regions that may otherwise be unsuitable based on climatic factors alone. This review highlights the need to incorporate the impact of the urban environment in attempts to model the potential distribution of Ae. aegypti and briefly discuss the potential for future technology to aid management and control of this widespread vector species.

The dengue vector Aedes aegypti: What comes next. Microbes Infect. Jan 20 2010. doi:10.1016/j.micinf.2009.12.011

Related:

• Population movement a critical factor in dengue virus spread
• Dengue Virus
• Rethinking dengue hemorrhagic fever
• Pathogenic Flaviviruses

Dengue fever is a major public health problem in many tropical regions of the world. It is a vector-borne disease, transmitted most often by the mosquito Aedes aegypti. According to the WHO, the prevalence of dengue is highest in tropical areas of Asia and the Americas, with 50-100 million estimated cases of dengue fever and 250,000-500,000 cases of dengue hemorrhagic fever occurring annually worldwide as explosive outbreaks in urban areas.

In Brazil, three dengue virus serotypes (DENV) have been introduced in the past three decades. In 2007-2008, a dengue fever epidemic in Rio de Janeiro led to 240 deaths registered (100 deaths due to dengue hemorrhagic fever and 140 due to other dengue-related complications). This populous city presents highly favorable conditions for transmission of dengue. Dengue surveillance and control in large urban areas with high levels of dengue transmission pose important challenges. Therefore, consistent knowledge of the dynamics of this disease that integrates epidemiological and entomological data is essential.

Human movement is a key factor of dengue virus inflow in Rio de Janeiro, Brazil. The results published in a new paper, based on data from a severe epidemic in 2007-2008, contribute to new understanding on the dynamics of dengue fever in the second largest city in Brazil. This research combines data on dengue fever seroprevalence, recent dengue infection, and vector density in three neighborhoods of Rio de Janeiro: an urban, a suburban, and a slum area. Serological surveys were conducted before and during the epidemic period. Entomological surveys consisted of weekly collections of A. aegypti eggs and adults from traps. This integrated entomological-serological survey showed evidence of silent transmission even during a severe epidemic. No association was observed between household infestation index and risk of dengue infection in these areas, raising new questions about where transmission occurs – in the household, at work or elsewhere. When combined, the neighborhood-specific seroprevalence maps correlated significantly higher risk with areas of intense people traffic. These results add to previous epidemiological studies of dengue virus infections and contribute to the understanding of A. aegypti habits. The conclusions may provide a basis for new studies that could further identify the higher seroprevalence risk areas and help to develop and implement dengue-control programs.

Spatial Evaluation and Modeling of Dengue Seroprevalence and Vector Density in Rio de Janeiro, Brazil. PLoS Negl Trop Dis 3(11): e545. doi:10.1371/journal.pntd.0000545
Rio de Janeiro, Brazil, experienced a severe dengue fever epidemic in 2008. This was the worst epidemic ever, characterized by a sharp increase in case-fatality rate, mainly among younger individuals. A combination of factors, such as climate, mosquito abundance, buildup of the susceptible population, or viral evolution, could explain the severity of this epidemic. The main objective of this study is to model the spatial patterns of dengue seroprevalence in three neighborhoods with different socioeconomic profiles in Rio de Janeiro. As blood sampling coincided with the peak of dengue transmission, we were also able to identify recent dengue infections and visually relate them to Aedes aegypti spatial distribution abundance. We analyzed individual and spatial factors associated with seroprevalence using Generalized Additive Model (GAM). Three neighborhoods were investigated: a central urban neighborhood, and two isolated areas characterized as a slum and a suburban area. Weekly mosquito collections started in September 2006 and continued until March 2008. In each study area, 40 adult traps and 40 egg traps were installed in a random sample of premises, and two infestation indexes calculated: mean adult density and mean egg density. Sera from individuals living in the three neighborhoods were collected before the 2008 epidemic (July through November 2007) and during the epidemic (February through April 2008). Sera were tested for DENV-reactive IgM, IgG, Nested RT-PCR, and Real Time RT-PCR. From the before– after epidemics paired data, we described seroprevalence, recent dengue infections (asymptomatic or not), and seroconversion. Recent dengue infection varied from 1.3% to 14.1% among study areas. The highest IgM seropositivity occurred in the slum, where mosquito abundance was the lowest, but household conditions were the best for promoting contact between hosts and vectors. By fitting spatial GAM we found dengue seroprevalence hotspots located at the entrances of the two isolated communities, which are commercial activity areas with high human movement. No association between recent dengue infection and household’s high mosquito abundance was observed in this sample. This study contributes to better understanding the dynamics of dengue in Rio de Janeiro by assessing the relationship between dengue seroprevalence, recent dengue infection, and vector density. In conclusion, the variation in spatial seroprevalence patterns inside the neighborhoods, with significantly higher risk patches close to the areas with large human movement, suggests that humans may be responsible for virus inflow to small neighborhoods in Rio de Janeiro. Surveillance guidelines should be further discussed, considering these findings, particularly the spatial patterns for both human and mosquito populations.

Related:

• Dengue Virus
• Rethinking dengue hemorrhagic fever
• Pathogenic Flaviviruses

Dengue virus infection usually causes a severe flu like illness, although symptoms may be mild in young children. DHF, however, is a severe and sometimes fatal complication of dengue virus infection that affects about half a million people every year after infection with any one of the four dengue virus (DENV) serotypes. DHF patients usually fall into two groups; children and adults who become infected with a second dengue virus serotype after an initial primary dengue virus infection with a different serotype, and infants with primary dengue virus infections born to mothers who have some dengue virus immunity. The widely accepted explanation for the pathogenesis of DHF in these settings, particularly during infancy, is antibody-dependent enhancement (ADE) of DENV infection.

Researchers conducted a prospective nested case-control study of DENV infections during infancy. Clinical data and blood samples were collected from 4,441 mothers and infants in up to two pre-illness study visits, and surveillance was performed for symptomatic and inapparent DENV infections. Pre-illness plasma samples were used to measure the associations between maternally derived anti-DENV3 antibody-neutralizing and enhancing capacities at the time of DENV3 infection and development of infant DHF. The study examined 60 infants with DENV infections across a wide spectrum of disease severity. DENV3 was the predominant serotype among the infants with symptomatic (35/40) and inapparent (15/20) DENV infections, and 59/60 infants had a primary DENV infection. The estimated in vitro anti-DENV3 neutralizing capacity at birth positively correlated with the age of symptomatic primary DENV3 illness in infants. At the time of symptomatic DENV3 infection, essentially all infants had low anti-DENV3 neutralizing activity and measurable DENV3 ADE activity. The infants who developed DHF did not have significantly higher frequencies or levels of DENV3 ADE activity compared to symptomatic infants without DHF. A higher weight-for-age in the first 3 mo of life and at illness presentation was associated with a greater risk for DHF from a primary DENV infection during infancy. This prospective nested case-control study of primarily DENV3 infections during infancy has shown that infants exhibit a full range of disease severity after primary DENV infections.

The current model for development of DHF in infants around 6 months old is that anti-dengue virus antibodies transferred from a dengue-immune mother to her child somehow enhance dengue virus infection, resulting in more severe symptoms (the  antibody-dependent enhancement  model). These results support an initial in vivo protective role for maternally derived antibody. There was no significant association between DENV3 ADE activity at illness onset and the development of DHF compared with less severe symptomatic illness. The results of this study should encourage rethinking or refinement of the current ADE pathogenesis model for infant DHF and stimulate new directions of research into mechanisms responsible for the development of DHF during infancy.

A Prospective Nested Case-Control Study of Dengue in Infants: Rethinking and Refining the Antibody-Dependent Enhancement Dengue Hemorrhagic Fever Model. PLoS Med 6(10): e1000171 doi:10.1371/journal.pmed.1000171

Related:

• Dengue Virus
• Dengue virus infection activates the unfolded protein response
• Pathogenic Flaviviruses

Platelet-activating factor (PAF) is a potent and versatile mediator of inflammation that is produced by numerous cell types and tissues, and particularly by leukocytes. PAF acts on a single receptor (PAFR) that may be expressed on the plasma membrane or the outer leaflet of the nucleus of various cell types, but especially leukocytes, platelets, and endothelial cells. The endogenous release of PAF may account for several of the manifestations of acute inflammation. The administration of PAF to rodents or humans reproduces many features of the systemic inflammatory response syndrome, including hypotension, increased vascular permeability, hemoconcentration, cytokine release, and shock.

Dengue fever and dengue shock or hemorrhagic syndromes (DSS) are mosquito-borne diseases caused by 1 of 4 serotypes of Dengue virus (DEN 1–4). There are an estimated 50–100 million cases of dengue fever and 20,000 deaths annually mostly in tropical and subtropical regions of the world. The large number of infected individuals, the lack of clinical or laboratory markers that indicate which patients will develop severe disease, and the lack of specific treatment place an enormous burden on health systems of low-income countries. Treatment of dengue fever and of the severe forms of dengue infection is supportive only.

DSS is defined as fever with hemorrhage manifestations, thrombocytopenia, and hemoconcentration or other signs of plasma leakage. Severe dengue infection is characterized by increased vascular permeability, altered number of leucocytes, increased hematocrit, thrombocytopenia, and varying degree of hemorrhage. The extensive plasma leakage in various serous cavities of the body may result in profound and intractable shock. Hemorrhage, when it occurs, may contribute to hypotension. These features remarkably resemble the pathophysiological changes observed after the systemic activation of PAFR in experimental animals.

This data provide strong evidence of the involvement of PAFR in the pathogenesis of experimental dengue infection in mice. It also suggest that therapeutic use of PAFR antagonists may be feasible in humans, as this class of compounds prevents the manifestations and lethality of dengue infection even when given days after the onset of disease. The PAFR antagonist UK-74,505 used in this study has a good safety profile and has been shown to effectively block the PAFR in humans when given orally. It is possible that therapeutic use of PAFR antagonists in humans may ameliorate manifestations of dengue and prevent evolution to severe disease.

Essential role of platelet-activating factor receptor in the pathogenesis of Dengue virus infection. PNAS USA July 30, 2009. doi: 10.1073/pnas.0906467106
Severe dengue infection in humans causes a disease characterized by thrombocytopenia, increased levels of cytokines, increased vascular permeability, hemorrhage, and shock. Treatment is supportive. Activation of platelet-activating factor (PAF) receptor (PAFR) on endothelial cells and leukocytes induces increase in vascular permeability, hypotension, and production of cytokines. We hypothesized that activation of PAFR could account for the major systemic manifestations of dengue infection. Inoculation of adult mice with an adapted strain of Dengue virus caused a systemic disease, with several features of the infection in humans. In PAFR−/− mice, there was decreased thrombocytopenia, hemoconcentration, decreased systemic levels of cytokines, and delay of lethality, when compared with WT infected mice. Treatment with UK-74,505, an orally active PAFR antagonist, prevented the above-mentioned manifestations, as well as hypotension and increased vascular permeability, and decreased lethality, even when started 5 days after virus inoculation. Similar results were obtained with a distinct PAFR antagonist, PCA-4246. Despite decreased disease manifestation, viral loads were similar (PAFR−/−) or lower (PAFR antagonist) than in WT mice. Thus, activation of PAFR plays a major role in the pathogenesis of experimental dengue infection, and its blockade prevents more severe disease manifestation after infection with no increase in systemic viral titers, suggesting that there is no interference in the ability of the murine host to deal with the infection. PAFR antagonists are disease-modifying agents in experimental dengue infection.

Related:

• Dengue Virus
• Dengue virus infection activates the unfolded protein response

To control mosquito-borne diseases like dengue fever, researchers need to look at the behavior of people, not just the insect that transmits the disease. Vector-borne diseases constitute a largely neglected and enormous burden on public health in many resource-challenged environments, demanding efficient control strategies that could be developed through improved understanding of pathogen transmission. Human movement – which determines exposure to vectors – is a key behavioral component of vector-borne disease epidemiology that is poorly understood.

A new paper attempts to develop a conceptual framework to organize past studies by the scale of movement and then examine movements at fine-scale – i.e. people going through their regular, daily routine – that determine exposure to insect vectors for their role in the dynamics of pathogen transmission. The authors develop a model to quantify risk of vector contact across locations people visit, with emphasis on mosquito-borne dengue virus in the Amazonian city of Iquitos, Peru.

An example scenario illustrates how movement generates variation in exposure risk across individuals, how transmission rates within sites can be increased, and that risk within sites is not solely determined by vector density, as is commonly assumed. This analysis illustrates the importance of human movement for pathogen transmission, yet little is known – especially for populations most at risk to vector-borne diseases (e.g. dengue, leishmaniasis, etc.). The authors outline several important considerations for designing epidemiological studies to encourage investigation of individual human movement, based on this experience studying dengue.

The incidence of dengue fever in Iquitos has varied from around five percent to over 30 percent after new virus serotype introductions. There is no vaccine and no cure for dengue, which is transmitted by the tiger-striped, day-biting mosquito, Aedes aegypti. To track individual human movement, the research team used satellite-based global positioning system (GPS) and culturally-sensitive interviews that were developed by the team. The researchers developed a conceptual model showing that the relevance of human movement at a particular scale depends on vector behavior. Focusing on Aedes aegypti, they illustrated how vector-biting behavior combined with fine-scale movements of individual humans engaged in daily routines can influence transmission. They also outlined several considerations for designing epidemiological studies to encourage studies of individual human movement. They hope to arrive at a better notion of the spatial scale on which dengue transmission occurs and from an operational standpoint, at what scale to focus interventions. Another aim is to encourage researchers of other mosquito-borne diseases, such as malaria, to perform more incisive examination of individual movements.

The Role of Human Movement in the Transmission of Vector-Borne Pathogens. PLoS Negl Trop Dis 3(7): e481 doi:10.1371/journal.pntd.0000481
Human movement is a key behavioral factor in many vector-borne disease systems because it influences exposure to vectors and thus the transmission of pathogens. Human movement transcends spatial and temporal scales with different influences on disease dynamics. Here we develop a conceptual model to evaluate the importance of variation in exposure due to individual human movements for pathogen transmission, focusing on mosquito-borne dengue virus. We develop a model showing that the relevance of human movement at a particular scale depends on vector behavior. Focusing on the day-biting Aedes aegypti, we illustrate how vector biting behavior combined with fine-scale movements of individual humans engaged in their regular daily routine can influence transmission. Using a simple example, we estimate a transmission rate (R0) of 1.3 when exposure is assumed to occur only in the home versus 3.75 when exposure at multiple locations – e.g. market, friends – due to movement is considered. Movement also influences for which sites and individuals risk is greatest. For the example considered, intriguingly, our model predicts little correspondence between vector abundance in a site and estimated R0 for that site when movement is considered. This illustrates the importance of human movement for understanding and predicting the dynamics of a disease like dengue. To encourage investigation of human movement and disease, we review methods currently available to study human movement and, based on our experience studying dengue in Peru, discuss several important questions to address when designing a study. Human movement is a critical, understudied behavioral component underlying the transmission dynamics of many vector-borne pathogens. Understanding movement will facilitate identification of key individuals and sites in the transmission of pathogens such as dengue, which then may provide targets for surveillance, intervention, and improved disease prevention.

Related:

• Dengue Virus
• Pathogenic Flaviviruses
• Changing patterns of chikungunya virus

Aedes (Stegomyia) aegypti (Linneaus) is an important vector of dengue and other arboviruses. Despite its limited flight dispersal capability, its close association with humans and its desiccation-resistant eggs have facilitated many long distance dispersal events within and between continents, allowing it to expand its range globally from its origin in Africa. Its global emergence and resurgence can be attributed to factors including urbanisation, transportation, changes in human movement, and behaviour, resulting in dengue running second to malaria in terms of human morbidity and mortality. Global historical collections and laboratory experiments on this well studied vector have suggested its distribution is limited by the 10°C winter isotherm, while a more recent and complex stochastic population dynamics model analysis suggests the temperature’s limiting value to be more towards the 15°C yearly isotherm. While historical surveys in Australia have indicated that Ae. aegypti occurred over much of the continent, its range has receded from Western Australia, the Northern Territory and New South Wales (NSW) over the last 50 years. It is now only found in Queensland, although recent incursions into the Northern Territory have required costly eradication strategies. The significant reduction in vector distribution has been attributed to a combination of events including the introduction of reticulated water, which reduced the domestic water storage requirements of households that had provided stable larval sites, as well as the removal of the railway-based water storage containers hypothesised as being responsible for the long distance dispersal.

“Drought-proofing” Australia’s urban regions by installing large domestic water tanks may enable the dengue mosquito Ae. aegypti to regain its foothold across the country and expand its range of possible infections. A new paper challenges the common assumption that climate change will drive the spread of this mosquito, suggesting instead that the real driver is human behavior. The study combines current and forecasted climate change conditions with historical epidemics to reveal the risk of dengue infections in all capital cities around Australia by 2050. Researchers developed and critically assessed their models to project the distribution of the mosquito in 2030 and 2050. Currently, dengue fever occurs in Queensland only. However, the implementation of new water tanks, combined with already warm summer temperatures, could enable the mosquito to re-emerge and further its current reach. Dengue risks will not be driven directly by warmer temperatures or changes in rainfall patterns. Australian summers already provide ideal conditions for dengue transmission around the country, but the introduction of government-subsidized water storage devices now adds the ideal breeding ground for the dengue mosquito to re-emerge. While research is properly focused on the impact of anthropogenic climate change, this study highlights the need to look also at our responses to those changes and the outcomes they generate. The current dengue fever epidemic in far north Queensland is approaching 1,000 reported cases over the summer of 2008-2009.

Australia’s Dengue Risk Driven by Human Adaptation to Climate Change. 2009 PLoS Negl Trop Dis 3(5): e429
The reduced rainfall in southeast Australia has placed this region’s urban and rural communities on escalating water restrictions, with anthropogenic climate change forecasts suggesting that this drying trend will continue. To mitigate the stress this may place on domestic water supply, governments have encouraged the installation of large domestic water tanks in towns and cities throughout this region. These prospective stable mosquito larval sites create the possibility of the reintroduction of Ae. aegypti from Queensland, where it remains endemic, back into New South Wales and other populated centres in Australia, along with the associated emerging and re-emerging dengue risk if the virus was to be introduced. Having collated the known distribution of Ae. aegypti in Australia, we built distributional models using a genetic algorithm to project Ae. aegypti’s distribution under today’s climate and under climate change scenarios for 2030 and 2050 and compared the outputs to published theoretical temperature limits. Incongruence identified between the models and theoretical temperature limits highlighted the difficulty of using point occurrence data to study a species whose distribution is mediated more by human activity than by climate. Synthesis of this data with dengue transmission climate limits in Australia derived from historical dengue epidemics suggested that a proliferation of domestic water storage tanks in Australia could result in another range expansion of Ae. aegypti which would present a risk of dengue transmission in most major cities during their warm summer months. In the debate of the role climate change will play in the future range of dengue in Australia, we conclude that the increased risk of an Ae. aegypti range expansion in Australia would be due not directly to climate change but rather to human adaptation to the current and forecasted regional drying through the installation of large domestic water storing containers. The expansion of this efficient dengue vector presents both an emerging and re-emerging disease risk to Australia. Therefore, if the installation and maintenance of domestic water storage tanks is not tightly controlled, Ae. aegypti could expand its range again and cohabit with the majority of Australia’s population, presenting a high potential dengue transmission risk during warm summers.

Related:

• Pathogenesis and prevention of dengue virus infection
• Dengue Virus
• Clustering of dengue virus infections
• Dissecting the Cell Entry Pathway of Dengue Virus
• A new Arenavirus is responsible for deaths of three transplant recipients in Australia