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HEALTH

Dengue - A (Very Brief) Introduction

Written by Dr Kirubakaran

19—MAY—2021 20:25 GMT
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It's worrying...

Malaysians have learnt to co-exist with arboviruses (the kind of virus transmitted by insects) to a great degree. You see windows being shut by nightfall, mosquito coils burning outdoors and a taboo of exercising outdoors after sunset. Dengue is one such example. However, it extends beyond Malaysia; the WHO estimates that just under 4 billion people are at risk of infection with dengue viruses. Alarmingly, 70% of the global disease burden is represented by Asian countries (1). 

 

In addition, dengue is beginning to affect countries with temperate climates, such as in Europe and Australia.2 While the virus is not naturally present there, it is imported via international travellers, who get infected in countries endemic with dengue. Before pressing on, it is important to note that the insect that transmits dengue – Aedes mosquitoes – are also known as vectors. If the vector is naturally present (albeit in low numbers) and able to survive in these somewhat temperate climates, dengue virus can be transmitted onwards to other people, establishing its own vicious transmission cycle which will only continue to worsen, if public health control measures fail. 

 

While international travel isn’t common during the pandemic, this now documented capacity of the virus to establish infections in novel areas is worrying. For the combined reasons above, it is imperative that we digest the factors that drive dengue transmission, the reason it is deadly and how we – the collective public - can control this deadly disease. 

How does dengue get transmitted?

Before the virus can affect humans, dengue virus firstly infects its vector – Aedes mosquitoes. There, the viral particles multiply before localising to the salivary gland of the mosquito. When a female mosquito then bites a human (only females do so), these virus particles are transferred into the human tissue via its saliva (3,4). Thus, anything that allows mosquitoes to thrive allows dengue virus to thrive. Understanding these factors can enable apt public health control measures.

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Transmission cycle of dengue.
Image from Nature.com

1. Environmental factors

The environmental factors include temperature, rainfall, air quality and humidity. These contribute to increased dengue incidence:

- Tropical temperatures

- Increased rainfall

- Increased humidity

- Improved air quality (although more research is required)

 

These conditions are optimal for Aedes mosquitoes to thrive (5–8). An increase in humidity is hypothesised to increase the lifespan of the vector enabling an increase in biting frequency. Bearing in mind that Aedes mosquitoes breed in stagnant water, increased rainfall allows for the creation of potential breeding sites i.e. flowerpots, clogged drains, and buckets. Unplanned urban development i.e., improperly built sewage and drains and improper waste management that often is present in many cities which only contributes to its increasing endemicity (9).

2. Dengue serotypes

It is important to consider that what we refer to as ‘dengue virus’ actually comprises multiple serotypes (a serotype are groups within a single species of a microorganism such as bacteria or virus that share a distinct surface protein). With dengue there is DENV1, DENV2, DENV3 and DENV4 (10).

 

So, what does this all mean? Let’s dive into a few details about viral particles: 

 

Every viral particle contains nucleic acids (this is the stuff in our bodies – DNA and RNA), of which they can be split into RNA viruses or DNA viruses. What is the link between these components? Simply put:

DNA → RNA → Protein Sequence ⟹
Gives the individual cell its function

Over thousands of years and mutations (especially by RNA viruses) this can result in individual dengue viruses that are different to each other. This can result in different serotypes, and therefore our immune system might be prepared to fight one, but not new ones if we are infected by them. 

 

This is one of the reasons why a vaccine is difficult to design and why dengue appears to be ‘worse’ on the second and subsequent times an individual gets infected (11,12). 

 

In addition to that, dengue infections are asymptomatic! If an individual gets infected the first time (primary infection), which in most cases is asymptomatic, they are thought to possess lifelong immunity to that serotype. In addition, following a primary infection with one serotype, an individual would obtain transient protection from all serotypes which wanes and decays over time. Therefore, lifelong immunity one serotype of a virus does not mean you’re immune to the other types (1). 

 

Unfortunately, just like COVID-19, it is thought that asymptomatic infections are to be the key drivers of increased dengue transmission, as infected individuals are bitten by mosquitoes who spread the virus to non-infected individuals. 

 

The critical symptoms and awful presentation of dengue – dengue haemorrhagic shock – occurs most commonly when an individual gets infected with a different serotype. The question is: why are our neutralising antibodies effective against one serotype but not others? 

 

In fact, they perform a role that is worse than doing nothing – these ‘non-neutralising’ antibodies aid the virus in attacking our own bodies. This is called antibody-dependent enhancement (ADE). This is where these non-specific antibodies somehow bind to the novel (different serotype) dengue virus but don’t remove it. Nonetheless, these bound non-neutralising antibodies engage our circulating monocytes. These are a type of a cell in our immune system that degrade viral particles. However instead of doing so, the virus corrupts these monocytes (11). An analogy would be this: 

A spy (dengue virus) pretends to be apprehended by the military (monocytes), who assumes the prisoner is now no longer a threat. So, they bring the spy along their duty routes (body circulatory system). All this while, the spy corrupts each and every military personnel (other cells), until they defect and no longer serve their general (our body). The spy is then able to meet other troops (other cells) and corrupt (infect) them.

This essentially allows the virus to replicate and produce more of its own kind more efficiently, and therefore cause more dangerous symptoms. This is why there are sharp increases in dengue cases every few years. A new serotype that the population is not immune to would result in novel infections and an alarming and significant increase in incidence.

What can I do to protect myself?

Any two locations, even within individual countries, can differ tremendously in its climatic factors and population distribution. This can make implementing public health measures difficult, but what can we, as individuals, do? 

 

- Keep ourselves informed of any local outbreaks in our states/districts and of local fogging in our neighbourhoods

- If you see a pot full of water, empty it. 

- If you see a clogged drain close to home, clear it to avoid accumulation of stagnant water. 

- Remember, Aedes mosquitoes are daytime feeders (1) - anytime from dawn to dusk (with peak biting times at dawn and at evenings just before dusk). If you exercise outdoors, aim to do so at the right hours, wear long-sleeved clothing and burn mosquito coils (it might help!) (13). 

- Aedes mosquitoes live indoors (behind curtains, underneath beds and cupboards). A good clean of the house once in a while may help clear these pests.

 

Since any one of us could be asymptomatic carriers, keeping our surroundings clean and safe could protect the other members of our community. Remember, it only takes one mosquito bite to kill.

References

1. WHO. Dengue and severe dengue. (2020).

2. Schaffner, F. & Mathis, A. Dengue and dengue vectors in the WHO European region: Past, present, and scenarios for the future. The Lancet Infectious Diseases (2014) doi:10.1016/S1473-3099(14)70834-5.

3. Nature Education. Dengue Transmission. Scitable by Nat. Educ. (2014).

4. Salazar, M. I., Richardson, J. H., Sánchez-Vargas, I., Olson, K. E. & Beaty, B. J. Dengue virus type 2: Replication and tropisms in orally infected Aedes aegypti mosquitoes. BMC Microbiol. (2007) doi:10.1186/1471-2180-7-9.

5. Hii, Y. L., Zhu, H., Ng, N., Ng, L. C. & Rocklöv, J. Forecast of Dengue Incidence Using Temperature and Rainfall. PLoS Negl. Trop. Dis. (2012) doi:10.1371/journal.pntd.0001908.

6. Promprou, S., Jaroensutasinee, M. & Jaroensutasinee, K. Climatic factors affecting dengue haemorrhagic fever incidence in Southern Thailand. Dengue Bull. (2005) doi:10.2004/wjst.v2i1.175.

7. Ruzman, N. S. L. N. & Rahman, H. A. The association between climatic factors and dengue fever: A study in Subang Jaya and Sepang, Selangor. Malaysian J. Public Heal. Med. (2017).

8. Carneiro, M. A. F. et al. Environmental factors can influence dengue reported cases. Rev. Assoc. Med. Bras. (2017) doi:10.1590/1806-9282.63.11.957.

9. Gubler, D. Dengue, urbanization and globalization: The unholy trinity of the 21st century. Int. J. Infect. Dis. (2012) doi:10.1016/j.ijid.2012.05.009.

10. Nature Education. Dengue Viruses. Scitable by Nat. Educ. (2014).

11. Nature Education. Host Response to the Dengue Virus. Scitable by Nat. Educ. (2014).

12. Ferguson, N. M. et al. Benefits and risks of the sanofi-pasteur dengue vaccine: Modeling optimal deployment. Science (80-. ). (2016) doi:10.1126/science.aaf9590.

13. Ogoma, S. B., Moore, S. J. & Maia, M. F. A systematic review of mosquito coils and passive emanators: Defining recommendations for spatial repellency testing methodologies. Parasites and Vectors (2012) doi:10.1186/1756-3305-5-287.

14. Bowman, L. R., Donegan, S. & McCall, P. J. Is Dengue Vector Control Deficient in Effectiveness or Evidence?: Systematic Review and Meta-analysis. PLoS Negl. Trop. Dis. (2016) doi:10.1371/journal.pntd.0004551.