There is only a limited understanding of the dengue virus and its pathogenesis due to challenges faced in finding a suitable animal model to study. Regular Dengue fever is not necessarily fatal and has similar symptoms to the flu or other viral infections, which makes it difficult to recognise and study, especially in third-world countries in which it is most prevalent. Dengue Haemorrhagic fever, however, is a complication that can arise from the dengue virus which is fatal 50% of the time when left untreated. This is characterised by more severe symptoms, ultimately leading to Dengue Shock Syndrome (excessive bleeding, shock and death). Hence, it is more easily diagnosed, but as the availability of suitable laboratories and technology for studying this virus is limited in many third-world countries, autopsies are rarely conducted; in fatal cases, most families opt for burial or cremation to prevent the potential spread of the virus. Moreover, the small number of live patients studied with this disease are often in the later stages of infection, which means there are large gaps in the knowledge its development.
However, as a virus, it is known to infect cells using similar methods to other viruses:
The virus attaches to the surface of a cell
The virus enters the cytoplasm and fuses with the endoplasmic reticulum.
The viral RNA is translated as a long polypeptide which is cut into 10 proteins, which are responsible for the replication of the virus
Viral components are rapidly replicated inside the cell and assembled on the surface of the endoplasmic reticulum.
The immature viruses are then transported to the Golgi Apparatus in transport vesicles, where they complete their growth into mature viruses
The completed viruses then exit the cell to infect other cells
Dengue fever is a mosquito-borne disease that enters the body when a mosquito carrier of the dengue virus feeds on a human, injecting the virus into the bloodstream through the epidermis and dermis layers of the skin. The dengue virus is known to target and replicate in immune cells, initially the dendritic epidermal cells (skin cells with dendrites, specifically immature Langerhans cells) and keratinocytes (keratin producing skin cells) located in the skin. The virus then travels to the lymph nodes inside the infected epidermal cells until they are ingested by phagocytic monocytes and macrophages, immune cells that engulf harmful viruses and bacteria and digest them. However, these cells become infected by the virus, and hence the virus is disseminated through the lymph nodes and soon the entire lymphatic system. Dengue virus has also been known to target other cells in the body, including mononuclear spleen, bone marrow and blood cells. After these are infected, apoptosis (normal, programmed cell death) is induced, and the infected dendritic epidermal cells cause inflammation and haemostasis, preventing the flow of blood in the blood vessels. Henceforth, dengue fever occurs for a period of 10 days, but recovery from the symptoms may take longer.
Dengue fever is not contagious, as it usually requires the virus to be injected through the skin by a vector for one to develop this disease. Nevertheless, it can be spread through blood transfusion, but this is rare in third-world countries in which the virus is most prevalent as blood donations are not common due to the lack of appropriate facilities. While only six cases of transfusion-related dengue fever have occurred, this may become a future problem if the dengue virus begins to emerge in higher-income countries.
Carriers of the dengue virus are the largest cause of its rapid spread; individuals infected by a vector have the capability to transmit the virus onto an uninfected mosquito that bites them, for a period of 4 to 12 days after the first symptoms arise. After the virus incubates in a mosquito, it will remain infectious for the rest of the mosquito’s life, allowing transmission to many people.
Of the people infected by a mosquito vector of the dengue virus, certain groups of people have been found to be greater at risk of developing dengue fever. Young children, the elderly and immune deficient people are at a greater risk of developing dengue haemorrhagic fever, however, all people can develop regular dengue fever from mosquitos containing the virus. While 80% of people infected with dengue virus are asymptomatic (show no symptoms), it is not yet clear why this occurs and whether it is an issue.
Dengue fever exists only where the vectors can survive, which is specific for its two main species of vectors, the Aedes aegypti and Aedes albopictus mosquitos. The Aedes aegypti mosquito is found mostly in tropical and subtropical areas, but can also live in some temperate regions. Urban habitats are most affected, as these provide optimal breeding grounds for this species. Humans are also their preferred host, which makes this species the most suitable for spreading dengue virus: dengue fever only affects humans. This mosquito inhabits most of Africa, South and Central America, South-East Asia, and Northern Australia, which are categorised by high humidity, high rainfall and high temperatures.
Aedes albopictus is another common vector of dengue virus that is highly adaptive to climate through hibernation and tolerance to freezing temperatures. This enables this species to survive in parts of Asia, South and North America and Europe which are more temperate. This mosquito is more prevalent in rural areas where it can feed off animals and some human hosts, but in urban areas, humans are the primary target. Despite having a longer lifespan than Aedes aegypti (a maximum of 65 days in comparison to 22 days), this mosquito is estimated to be approximately 69% less likely to feed off humans due to these behaviours.
The regions in which the dengue virus can be located are determined by the suitability of its vectors in different environmental conditions. Maximum and minimum temperatures are factors which influence the presence of dengue in some areas, as the virus and the vectors can only survive within specific ranges of temperatures. The highest transmission efficiency for the Aedes aegypti mosquito occurs when the maximum temperature is approximately 32ºC, however, at temperatures over 36ºC these mosquitos begin to die from the heat. Low minimum temperatures inhibit the feeding, movement, breeding and survival capabilities of these two mosquitos, however the Aedes aegypti is slightly more affected by cool weather, becoming less suitable for viral transmission at temperatures under 14ºC, compared with 13ºC for the Aedes albopictus mosquito.
Nevertheless, while an area may be in the acceptable range for the dengue virus, the humidity can affect the survivability of its vectors. Arid environments, such as those at high altitudes, or in deserts are substantially less favourable for these species of mosquito, which explains their absence in the Middle East and Northern Africa. However, in tropical and subtropical biomes with higher humidity, such as South-East Asia and Central America, the incidence of dengue fever is dramatically increased, showing that humidity relative to temperature certainly has a role in determining its prevalence.
Furthermore, levels of precipitation also have been shown to impact mosquito populations and hence the incidence of dengue fever. As shown in the graph, low annual rainfall produces a lower risk of infection, while amounts of around 550mm are optimal: the pooling water creates suitable habitats for mosquito breeding. Higher levels (>650mm) are unsuitable, as the excess rain washes away these said breeding-sites.
On the topic of climate change, this likelihood will certainly impact the distribution of dengue cases around the world. Higher minimum temperatures will be benefit vector survival in currently temperate regions, enabling greater success, but in areas with already high maximum temperatures, vector mortality will rise and decrease dengue fever incidence. Dropping annual precipitation will reduce the number of available habitats as drought becomes increasingly more common, and hence the humidity will also be decreased over time. As discussed before, these factors are responsible for influencing the prevalence of said mosquitos, and it is clear that climate change will ultimately damage the incidence of dengue fever in many areas.
Dengue fever becomes symptomatic after an incubation period of 4-10 days in the body, although it is predominantly asymptomatic, where no signs of the virus are manifested. This disease chills, rash, severe headaches, muscle and joint pain and high fever, in addition to other symptoms shown below (IN DIAGRAM).
Usually, the symptoms disappear within 2-7 days, but can occasionally lead on to severe or haemorrhagic dengue fever, which is potentially fatal and produces serious symptoms including excessive bleeding, vomiting, abdominal pain and shock, combined with those of regular dengue fever.
After being infected with dengue virus, one becomes immune to that specific strain for the rest of their life. However, if the same individual is subsequently infected by a different serotype of the virus, the result can be life threatening, as the body is only conditioned for the serotype it has experienced before. Dengue haemorrhagic fever often arises after recovery from regular dengue fever begins. Complications from this are potentially life-threatening; organ damage and failure, seizures, and Dengue Shock Syndrome, which is categorised by profuse bleeding, hypotension and shock, followed by death. However, if hospital treatment is initiated early, there is a significantly greater chance of recovery.
Treatment:
As of present, there are no effective treatment options for dengue fever. Neither are there any vaccination or prevention methods available in Australia. However, a vaccine called Dengvaxia has been approved for use in Brazil, Mexico and the Philippines, where dengue fever is endemic. This vaccine is based on the yellow fever vaccine, a virus similar to dengue, but with an envelope and membrane genetically engineered to resemble those of the four dengue serotypes (different strains of the virus, which all interact differently with the target cells). The vaccine prompts the body to create antibodies to combat the inactive viruses recognised by the body’s neutrophils to be dengue viruses from the specific arrangement of proteins in their viral envelope. Thus, when an individual inoculated against dengue virus develops the infection, their body will be more effective at combating dengue fever as it has already encountered and fought the virus before, albeit in a weakened form. Results have shown the efficacy of this virus to be 65.6% in people aged over 9 years, however it is less successful in younger children under 9 years and elderly people over 45, where only 44% of people are protected, as indicated during the vaccine’s third stage of clinical trials which began in 2010.
While other vaccines are currently in clinical development, Dengvaxia, despite being reasonably successful, has not been introduced in any other countries, and only in people aged from 9-45 years. Meanwhile, dengue fever, and especially dengue haemorrhagic fever is most prevalent in young children, so this current vaccine is not sufficient.
If one manages to contract dengue fever without the protection of the vaccine (or its unsuccessfulness), there are no effective treatments. Patients are suggested to drink plenty of fluids, rest, and take pain relievers containing acetaminophen (Paracetamol) to reduce the fever. Hospitalisation is recommended, especially in the case of dengue haemorrhagic fever, which has a mortality rate of 50% when left untreated. However, proper hospital care can reduce this rate to less than 5% and 1% for regular dengue fever through symptomatic treatments and monitoring.
Due to the lack of any effective medicines for treatment and the unavailability of a dengue fever vaccine outside of the three endemic countries— Brazil, Mexico and the Philippines— vector control is ultimately the primary option for dengue prevention and control. Individuals living or traveling to endemic dengue areas are advised to use insect repellents, stay indoors in air conditioned rooms, use bed nets if sleeping outside and wear long-sleeved clothing to limit the skin area where infection by a dengue-carrying mosquito can occur. Furthermore, the use of insecticides and the destruction of artificial breeding grounds for the mosquito vectors will assist the control of mosquito populations, but education on dengue fever prevention through these methods is overall the most promising pathway.
Responsibility:
Australia has a responsibility, as a privileged nation, to help nations inflicted dengue fever through education on vector control and prevention, in addition to continuing to search and develop effectual vaccines and medicines to treat this disease. According to the first Catholic Social Teaching Principle, The Dignity of the Human Person, it is the duty of this nation to preserve the dignity of all people which is inherent as a creation of God made in His own image. Dengue fever and dengue haemorrhagic fever are endemics that diminish and destroy the lives of people, and make the preservation of this fundamental entitlement impossible; the physical suffering engendered by this virus prevents people from living dignified lives.
The fifth principle, Preferential Option for the Poor, entails that Australia, being a wealthy nation, takes the needs of the poor and considers them most important. In the case of dengue fever, a predominantly third-world disease, Australia would need to provide support to endemic dengue areas where people often do not have the facilities to treat patients or conduct research. This could involve funding or the provision of qualified doctors or researchers with greater knowledge on this disease to assist in low-income areas rife with dengue fever. Researchers in Australia could also devote more time and effort to studying the dengue virus as a precursor for attempts to create drugs or vaccines. In doing this, Australia is considering the needs of the most vulnerable and underprivileged, thus fulfilling this Catholic Social Teaching Principle.
Conclusion:
The incidence of dengue fever, while still under research, has been shown to be influenced by various environmental factors including, but not limited to temperature, precipitation and humidity levels. Climate change proves to be influential in the spread of the dengue virus around the world, but this concerns the long-term and involves many over factors that require more research for any predictions. Dengue fever is indeed a growing problem, but it is hoped that through the implementation of new vaccines and medications for treatment, the lives of people in dengue-endemic third-world countries can be improved.