Introduction

Imagine that you are the Health Minister of Brazil, a country with an enormous population of about 220 million. In the past few months, your country has suffered 1 million registered cases and 214 deaths due to a disease called dengue. Your government’s public health system is struggling to keep up with the increasing cases. You cannot even ask your neighbouring country Peru for help as they are going through the same dengue crisis. How would you deal with this? Well, this scenario is not so imaginary. Brazil in 2024 had declared a health emergency due to the surge in dengue cases across the country.

Dengue is caused by an arbovirus which are viruses transmitted by mosquitoes, sandflies, and ticks. Arboviruses can also cause chikungunya and zika, which along with dengue are major obstacles for public health in the Americas. Arboviruses like dengue have been a major threat to society since 400 C.E, when the first case of dengue appeared in a Chinese Medical Encyclopedia. In the 15th century, as slave trade and travel increased in Africa, there was a rise in populations of arbovirus vectors. This led to the outbreak of numerous dengue epidemics in Asia, the Americas, and Africa during the 18th - 19th centuries. Now in 2023, over 4 million dengue cases have been reported in the Region of the Americas with dengue epidemics recurring every 3-5 years. Although arboviruses have been present for 10,000’s of years, and numerous efforts have been made to eradicate these arboviruses, as a journal article from “Current Opinion in Virology” rightly describes, staying ahead of viruses is a never-ending task.

Dengue and Infection

Dengue Virus or DEN-V is a single stranded RNA virus of the Flaviviridae family and is transmitted to humans by the bite of an infected female mosquito. There are four strains of the dengue virus namely DENV-1, DENV-2, DENV-3 and DENV-4. Dengue virus (DEN-V) infection symptoms show up 4 - 10 days after one is bitten, and include high fever (104° C), joint pain, vomiting, and headaches. Sometimes a more life- threatening form of dengue called dengue hemorrhagic fever (DHF) can occur which results in bleeding under the skin and blood in urine or stools. In severe cases, a patient may experience a sudden drop in blood pressure causing a shock, hence this disease is also called dengue shock syndrome (DSS). Vectors are organisms that transmit disease from one organism to another. The primary vector of DEN-V is Aedes aegypti.These mosquitoes get infected when they bite an individual who has been infected with DEN-V and spread the virus by their bites. Interestingly, it has been found that dengue can also pass from infected mother to fetus during pregnancy.

What happens inside the body when an infected mosquito bites an individual? First the virus enters the bloodstream and infects and replicates inside neighbouring skin cells called keratinocytes. DEN-V also infects Langerhans cells, a type of dendritic cell present in the skin, whose function is to detect pathogens like DEN-V and present a portion of the virus to other immune cells. Monocytes and macrophages are immune cells, responsible for ingesting and destroying the pathogen, however DEN-V targets and infects these immune cells, preventing them from performing their function. As these cells migrate to different parts of the body, the virus spreads and infects more and more cells, including those of the liver, spleen, lymph nodes and bone marrow.

The Immune Fight

Now that the virus has begun taking over your body, how does the immune system combat this?

Well, our immune system has several tricks up its sleeve. The infection of the virus sets off an acute inflammatory response with symptoms of heat, redness, pain, inflammation due to release of soluble cellular messengers called cytokines. Cytokines act on the hypothalamus, a brain structure that regulates body temperature, causing an increase in the body temperature, leading to fever, one of the main symptoms of dengue. Under fever conditions, viruses like DEN-V cannot replicate as efficiently. Cells infected with the DEN-V virus produce a type of cytokine called interferons, which are soluble proteins that interfere with the viral replication and thereby prevent the virus from spreading to uninfected cells. These interferons bind to an interferon (IFN) receptor present on the same infected cell (called autocrine effect) or on an uninfected cell. This binding causes the cell to acquire an antiviral state, which inhibits the virus’s ability to replicate and causes degradation of viral material. In the meanwhile, the Langerhans migrate from the site of infection to the lymph nodes in which they present a portion of the virus for activation of the immature immune cells. After a few days of DEN-V infection, the adaptive immune system is ready to start its fight against the virus, by activation of T and B cells. B cells secrete antibodies, mainly IgG and IgM, that recognize and neutralize DEN-V at sites of infection and Killer T cells directly kill any infected cells. Hence the innate and adaptive immune system work together to eliminate the DEN-V virus and patients usually recover from the virus in about a week.

What makes dengue such a persistent issue even today?

Aedes aegypti mosquitoes dwell in hot and humid regions between latitudes of 35 ° N and 35 ° S i.e. in tropical and subtropical regions and breed in stagnant water usually associated with human households to complete their lifecycle.

So how does understanding these vectors play a role in combating their transmission?

As the vector breeds in stagnant water, eliminating stagnant water sources, wearing full length clothes and using insect repellents to prevent mosquito bites can help curb their transmission. Additionally local governments can perform fumigation with insecticides in localities to prevent the breeding of mosquitoes. However, globally there has been a significant increase in dengue mainly due to the El Niño effect in 2023. El Niño is a natural phenomenon of the warming of the Pacific ocean surface temperature which results in higher temperatures of surrounding areas. Similarly, higher temperatures, and high rainfall resulting from climate change, increase the breeding range of these mosquitos to include places that were once too cold for them to breed, leading to increase in dengue cases even in non-endemic regions.

References

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