Mosquitoes, Dengue Fever, and the Quest for a Dengue Vaccine

Dengue fever is a viral infection that affects millions of people around the world every year. It is transmitted by the bite of infected mosquitoes, mainly the Aedes aegypti species, which are found in tropical and subtropical regions. Dengue fever can cause a range of symptoms, from mild to severe, and sometimes even fatal. There is no specific treatment or cure for dengue fever, and the only way to prevent it is to avoid mosquito bites and control the mosquito population. In this blog post, we will explore what dengue fever is, how it affects people, and what efforts are being made to develop a vaccine against it.

What is dengue fever?

Dengue fever is caused by one of four types of dengue virus (DENV), which belong to the flavivirus family. The virus enters the human body through the saliva of an infected mosquito, and then multiplies in various tissues and organs, especially the lymph nodes, spleen, liver, and blood vessels. The virus can also infect some immune cells, such as macrophages and dendritic cells, and interfere with their function.

The incubation period of dengue fever is usually 4–10 days, after which the symptoms may appear. According to the World Health Organization (WHO), about 25% of people infected with dengue virus develop symptoms, while the rest remain asymptomatic or have mild illness.

The symptoms of dengue fever include:

· High fever (40°C/104°F)

· Severe headache

· Pain behind the eyes

· Muscle and joint pains

· Nausea

· Vomiting

· Swollen glands

· Rash

These symptoms usually last for 2–7 days, and then subside. However, some people may experience a second phase of illness, known as severe dengue or dengue hemorrhagic fever (DHF). This occurs when the virus triggers a severe immune response that damages the blood vessels and causes bleeding, shock, organ failure, and death. The risk of severe dengue is higher for people who have been infected with a different type of dengue virus before, as this can cause a phenomenon called antibody-dependent enhancement (ADE), where the antibodies from the previous infection enhance the entry and replication of the new virus instead of neutralizing it.

The symptoms of severe dengue may include:

· Severe abdominal pain
· Persistent vomiting
· Rapid breathing
· Bleeding from the gums or nose
· Blood in the urine, stool or vomit
· Bleeding under the skin, which might look like bruising
· Difficult or rapid breathing
· Fatigue
· Irritability or restlessness

Severe dengue is a medical emergency that requires immediate hospitalization and supportive care. The fatality rate of severe dengue can be as high as 20%, but can be reduced to less than 1% with proper management.

How common is dengue fever?

Dengue fever is one of the most widespread mosquito-borne diseases in the world. According to WHO estimates, about half of the world's population is now at risk of dengue infection, with an estimated 100–400 million cases occurring each year. Dengue fever is endemic in more than 100 countries in Africa, Asia, Latin America, and the Caribbean. The disease is also expanding its geographic range due to factors such as urbanization, globalization, climate change, and lack of effective vector control.

The global burden of dengue fever has increased dramatically in recent decades. The number of cases reported to WHO increased from 505,430 in 2000 to 5.2 million in 2019. The number of deaths due to dengue fever also rose from 960 in 2000 to 4,032 in 2019. Dengue fever causes significant morbidity and mortality, especially among children and young adults. It also imposes a huge economic and social cost on affected countries and communities.

How can dengue fever be prevented?

There is currently no approved vaccine or medication that protects against dengue fever. The only way to prevent dengue fever is to avoid being bitten by mosquitoes and to take steps to reduce the mosquito population. Some of the strategies that can help prevent mosquito bites include:

· Using insect repellents containing DEET, picaridin or oil of lemon eucalyptus on exposed skin and clothing.
· Wearing long-sleeved shirts and long pants when outdoors.
· Staying indoors during peak mosquito activity hours (dawn and dusk).
· Installing screens on windows and doors to keep mosquitoes out.
· Sleeping under a mosquito net or in an air-conditioned room.
· Eliminating or covering any potential breeding sites for mosquitoes, such as containers that hold water, tires, flower pots, etc.

Some of the strategies that can help reduce the mosquito population include:

· Spraying insecticides or larvicides in areas where mosquitoes breed or rest.
· Introducing biological control agents, such as fish, bacteria, or fungi, that kill mosquito larvae or adults.
· Releasing genetically modified or sterile male mosquitoes that mate with wild females and reduce their offspring.
· Releasing Wolbachia-infected mosquitoes that reduce the ability of dengue virus to replicate and spread in the mosquito population.

These strategies require coordinated efforts from governments, communities, and individuals to be effective and sustainable.

What is the status of dengue vaccine development?

Several efforts are underway to develop a safe and effective vaccine against dengue fever. However, developing a dengue vaccine is challenging for several reasons, such as:

· The need to protect against all four types of dengue virus, which have different antigenic properties and can cause cross-reactive immune responses that may enhance disease severity.
· The lack of a reliable animal model that mimics human dengue infection and disease.
· The ethical and logistical difficulties of conducting large-scale clinical trials in endemic areas.

Despite these challenges, some progress has been made in dengue vaccine research. The first dengue vaccine to be licensed was Dengvaxia, developed by Sanofi Pasteur. Dengvaxia is a live attenuated tetravalent vaccine that contains four recombinant viruses derived from the yellow fever vaccine strain. Dengvaxia was approved in 2015 in Mexico and has since been authorized in several countries in Asia and Latin America. However, Dengvaxia has shown limited efficacy and safety issues in some populations. In 2017, it was found that Dengvaxia could increase the risk of severe dengue in people who had not been previously exposed to dengue virus. As a result, WHO recommended that Dengvaxia should only be used in people who have had a confirmed prior dengue infection.

Other dengue vaccines are currently in various stages of development and testing. Some of the promising candidates include:

· TAK-003: A live attenuated tetravalent vaccine developed by Takeda. TAK-003 has shown high efficacy and safety in phase 3 trials involving more than 20,000 children and adolescents in Asia and Latin America. TAK-003 is expected to be submitted for regulatory approval soon.

· TV003/TV005: A live attenuated tetravalent vaccine developed by the National Institutes of Health (NIH) and Butantan Institute. TV003/TV005 has shown high efficacy and safety in phase 2 trials involving more than 4,000 adults in Brazil. TV003/TV005 is currently undergoing phase 3 trials in Brazil, Thailand, Vietnam, Colombia, and Nicaragua.

· DENVax: A live attenuated tetravalent vaccine developed by Merck. DENVax has shown promising results in phase 1 trials involving more than 100 adults in the U.S. and Singapore. DENVax is currently undergoing phase 2 trials in Singapore, Thailand, Colombia, and Puerto Rico.

In addition to these live attenuated vaccines, other types of vaccines are also being explored, such as subunit vaccines, DNA vaccines, mRNA vaccines, viral vector vaccines, and nanoparticle vaccines. These vaccines may offer advantages such as improved stability, safety, immunogenicity, and scalability.

Conclusion

Dengue fever is a serious global health problem that affects millions of people every year. There is no specific treatment or cure for dengue fever, and the only way to prevent it is to avoid mosquito bites and control the mosquito population. Several efforts are underway to develop a safe and effective vaccine against dengue fever, but none have been approved yet. Until then, we need to continue to raise awareness and implement preventive measures to reduce the burden of this disease.

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