Sep 19, Kathmandu: Dengue infections are assuming alarming proportions in Nepal. There are signs that dengue is becoming an epidemic across the country. Twenty people including seven children have died from dengue in one and a half months across the country.

According to the vector control inspector of the Ministry of Health and Population Epidemiology and Communicable Disease Control Division (EDCD), 7 children under 14 years old, 10 people between 20 and 40 years old, and the remaining 40 years old have died so far. According to the source, until now, the number of deaths due to dengue infection has reached 20.

What Is Dengue?

Dengue (pronounced DENgee) fever is a painful, debilitating mosquito-borne disease caused by any one of four closely related dengue viruses. These viruses are related to the viruses that cause West Nile infection and yellow fever.

Similarly, dengue fever is a mosquito-borne tropical disease caused by the dengue virus. Symptoms typically begin three to fourteen days after infection.  Dengue is caused by a viral fevers virus that is mostly transmitted by the bite of female mosquitoes of the species Aedes genus (Aegypti and Albopictus).   These mosquitoes are also vectors of chikungunya, yellow fever, and Zika viruses. Dengue is widespread throughout the tropics, with local variations in risk influenced by climate parameters as well as social and environmental factors.

The mosquito becomes infected when it bites a person with the dengue virus in their blood. It can’t be spread directly from one person to another person. Dengue is caused by a virus of the Flaviviridae family and there are four distinct, but closely related, serotypes of the virus that cause dengue (DENV-1, DENV-2, DENV-3, and DENV-4). Recovery from infection is believed to provide lifelong immunity against that serotype.

However, cross-immunity to the other serotypes after recovery is only partial and temporary. Subsequent infections (secondary infection) by other serotypes increase the risk of developing severe dengue. Dengue has distinct epidemiological patterns, associated with the four serotypes of the virus. These can co-circulate within a region, and indeed many countries are hyper-endemic for all four serotypes.

Dengue has an alarming impact on both human health and the global and national economies. DENV is frequently transported from one place to another by infected travelers; when susceptible vectors are present in these new areas, there is the potential for local transmission to be established.

 Dengue symptoms range from none to serious flu-like symptoms. A small proportion of people develop severe dengue, which can be fatal. There are four closely related dengue viruses, which are called dengue serotypes. Although recovery from infection gives immunity from the same dengue serotype.

 It also increases the risk of severe dengue if people are later infected by a different serotype. Dengue is the most widely distributed mosquito-borne viral disease in the world. It continues to spread rapidly because of climate change, rapid urbanization, and population growth.

Outbreaks are usually seasonal, peaking during and after the rainy season. The World Health Organization classifies dengue as one of the top ten threats to public health.  The initial symptoms of dengue are fever, red and sore eyes, headache, stomach, joint and muscle pain, and lethargy. Dengue is fatal when a person who has been infected with one type of virus is bitten by a mosquito with another type of virus.

According to the fact sheet of the US-based Center for Disease Control and Prevention (CDC), the body's blood clotting (clotting) process is disordered due to dengue. In its malignant form, the entire body begins to bleed. Dengue fever can last for 5 to 7 days. In the case of dengue, a person's blood cells decrease and immunity decreases. As a result, people tend to learn.

Global Burden

The incidence of dengue has grown dramatically around the world in recent decades. A vast majority of cases are asymptomatic or mild and self-managed, and hence the actual numbers of dengue cases are under-reported. Many cases are also misdiagnosed as other febrile illnesses.

One modeling estimate indicates 390 million dengue virus infections per year (95% credible interval 284–528 million), of which 96 million (67–136 million) manifest clinically (with any severity of disease) [2]. Another study on the prevalence of dengue estimates that 3.9 billion people are at risk of infection with dengue viruses. Despite a risk of infection existing in 129 countries [3], 70% of the actual burden is in Asia.

The number of dengue cases reported to WHO increased over 8 fold over the last two decades, from 505,430 cases in 2000 to over 2.4 million in 2010, and 5.2 million in 2019. Reported deaths between the years 2000 and 2015 increased from 960 to 4032, affecting mostly the younger age group. The total number of cases seemingly decreased during the years 2020 and 2021, as well as for reported deaths. However, the data is not yet complete and the COVID-19 pandemic might have also hampered case reporting in several countries.

The overall alarming increase in case of numbers over the last two decades is partly explained by a change in national practices to record and report dengue to the Ministries of Health, and to the WHO. But it also represents government recognition of the burden, and therefore the pertinence to report dengue disease burden.

Distribution and outbreaks

Before 1970, only 9 countries had experienced severe dengue epidemics. The disease is now endemic in more than 100 countries in the WHO regions of Africa, the Americas, the Eastern Mediterranean, South-East Asia, and the Western Pacific. The Americas, South-East Asia, and Western Pacific regions are the most seriously affected, with Asia representing ~70% of the global burden of disease.

Not only is the number of cases increasing as the disease spreads to new areas including Europe, but explosive outbreaks are occurring. The threat of a possible outbreak of dengue now exists in Europe; local transmission was reported for the first time in France and Croatia in 2010 and imported cases were detected in 3 other European countries. In 2012, an outbreak of dengue on the Madeira islands of Portugal resulted in over 2000 cases and imported cases were detected in mainland Portugal and 10 other countries in Europe. Autochthonous cases are now observed on an annual basis in a few European countries.

The largest number of dengue cases ever reported globally was in 2019. All regions were affected, and dengue transmission was recorded in Afghanistan for the first time.  The American region alone reported 3.1 million cases, with more than 25,000 classified as severe. Despite this alarming number of cases, deaths associated with dengue were fewer than in the previous year.  

A high number of cases were reported in Bangladesh (101,000), Malaysia (131,000) Philippines (420,000), and Vietnam (320,000) in Asia. In 2020, dengue affected several countries, with reports of increases in the numbers of cases in Bangladesh, Brazil, Cook Islands, Ecuador, India, Indonesia, Maldives, Mauritania, Mayotte (Fr), Nepal, Singapore, Sri Lanka, Sudan, Thailand, Timor-Leste, and Yemen. Dengue continues to affect Brazil, India, Vietnam, the Philippines, the Cook Islands, Colombia, Fiji, Kenya, Paraguay, Peru, and, the Reunion islands, in 2021. 

The COVID-19 pandemic is placing immense pressure on health care and management systems worldwide. WHO has emphasized the importance of sustaining efforts to prevent, detect and treat vector-borne diseases during this pandemic such as dengue and other arboviral diseases, as case numbers increase in several countries and place urban populations at the highest risk for both diseases. The combined impact of the COVID-19 and dengue epidemics could have devastating consequences on the populations at risk.

Transmission

Transmission Through A Mosquito Bite

The virus is transmitted to humans through the bites of infected female mosquitoes, primarily the Aedes aegypti mosquito. Other species within the Aedes genus can also act as vectors but their contribution is secondary to Aedes aegypti.

After feeding on a DENV-infected person, the virus replicates in the mosquito midgut, before it disseminates to secondary tissues, including the salivary glands. The time it takes from ingesting the virus to actual transmission to a new host is termed the extrinsic incubation period (EIP).

The EIP takes about 8-12 days when the ambient temperature is between 25-28°C. Variations in the extrinsic incubation period are not only influenced by ambient temperature; a number of factors such as the magnitude of daily temperature fluctuation, virus genotype, and initial viral concentration also alter the time it takes for a mosquito to transmit the virus. Once infectious, the mosquito is capable of transmitting the virus for the rest of its life.

Human-To-Mosquito Transmission

Mosquitoes can become infected by people who are viremic with DENV. This can be someone who has a symptomatic dengue infection, someone who is yet to have a symptomatic infection (they are pre-symptomatic), but also people who show no signs of illness as well (they are asymptomatic).

Human-to-mosquito transmission can occur up to 2 days before someone shows symptoms of the illness, up to 2 days after the fever has resolved. The risk of mosquito infection is positively associated with high viremia and high fever in the patient; conversely, high levels of DENV-specific antibodies are associated with a decreased risk of mosquito infection (Nguyen et al. 2013 PNAS). Most people are viremic for about 4-5 days, but viremia can last as long as 12 days.

Maternal Transmission

The primary mode of transmission of DENV between humans involves mosquito vectors. However, the possibility of maternal transmission (from a pregnant mother to her baby). While vertical transmission rates appear low, the risk of vertical transmission is seemingly linked to the timing of the dengue infection during pregnancy. When a mother does have a DENV infection when she is pregnant, babies may suffer from pre-term birth, low birth weight, and fetal distress.

Other Transmission Modes

Rare cases of transmission via blood products, organ donation, and transfusions have been recorded. Similarly, the transovarial transmission of the virus within mosquitoes has also been recorded. 

Vector Ecology

The Aedes aegypti mosquito is considered the primary vector of DENV. It could breed in natural containers such as tree holes and bromeliads, but nowadays it has well adapted to urban habitats and breeds mostly in man-made containers including buckets, mud pots, discarded containers, used tyres, storm water drains, etc., thus making dengue an insidious disease in densely populated urban centers.

Ae. Aegypti is a day-time feeder; its peak biting periods are early in the morning and in the evening before sunset  Female Ae. aegypti frequently feed multiple times between each egg-laying period leading to clusters of infected individuals. Once a female has laid her eggs, these eggs can remain viable for several months in dry condition and will hatch when they are in contact with water.

Aedes albopictus, a secondary dengue vector, has spread to more than 32 states in the USA, and more than 25 countries in the European Region, largely due to the international trade in used tyres (a breeding habitat) and other goods (e.g. lucky bamboo).

It favors breeding sites close to dense vegetation including plantations which is linked to increased risk of exposure for rural workers such as those in rubber and palm oil plantation, but it is also found to be established abundantly in urban areas. Ae. albopictus is highly adaptive. Its geographical spread is largely due to its tolerance to colder conditions, as an egg and adult. 

Similar to Ae. aegypti, Ae. albopictus is also a day biter and it has been implicated as the primary vector of DENV in a limited number of outbreaks, where Aedes aegypti is either not present, or present in low numbers. Similarly, dengue is a rapidly emerging disease in Nepal. The first dengue case was reported in the Chitwan district by a foreigner in 2004. Since then an increasing number of dengue cases have been reported in many urban cities of Nepal including several dengue outbreaks.

 Dengue is one of the rapidly emerging mosquito-borne viral diseases causing a serious problem in the lowland area in Nepal since 2006. Dengue fever is considered a year-round threat in Nepal, with the highest risk occurring from June through September. Authorities identified roughly 424 cases of dengue fever in 2021, 17,992 cases in 2019, and 811 cases in 2018.

The disease is now expanding to other areas including the hilly region and has been established as an endemic disease in Nepal. Nepal has experienced several outbreaks of dengue in recent years across many provinces in the country, requiring hospitalization of dengue cases and posing an economic burden to the patients and the health system. Timely prevention, proper case management, and rapid vector control are crucial to reducing the adverse impact of the diseases.

Symptoms of Dengue Fever

Symptoms which usually begin four to six days after infection and last for up to 10 days may include

• Sudden High Fever 
• Severe headaches  
• Pain behind the eyes  
• Severe joint and muscle pain  
• Fatigue
• Nausea 
• Vomiting 
• Skin Rash  which appears two to five days after the onset of fever
• Mild bleeding (such as a nose bleed, bleeding gums, or easy bruising)

Sometimes, symptoms are mild and can be mistaken for those of the flu or another viral infection. Younger children and people who have never had the infection before tend to have milder cases than older children and adults.

However, serious problems can develop. These include dengue hemorrhagic fever, a rare complication characterized by high fever damage to lymph and blood vessels, bleeding from the nose and gums, enlargement of the liver, and failure of the circulatory system.

The symptoms may progress to massive bleeding, shock, and death. This is called dengue shock syndrome (DSS). People with weakened immune systems as well as those with a second or subsequent dengue infection are believed to be at greater risk for developing dengue hemorrhagic fever.

Diagnosing Dengue Fever

Doctors can diagnose dengue infection with a blood test to check for the virus or antibodies to it. If you become sick after traveling to a tropical area, let your doctor know. This will allow your doctor to evaluate the possibility that your symptoms were caused by a dengue infection.

Treatment for Dengue Fever

There is no specific medicine to treat dengue infection. If you think you may have dengue fever, you should use pain relievers with acetaminophen and avoid medicines with aspirin which could worsen bleeding. You should also rest, drink plenty of fluids, and see your doctor. If you start to feel worse in the first 24 hours after your fever goes down, you should get to a hospital immediately to be checked for complications.

Risk factors

Previous infection with DENV increases the risk of the individual developing severe dengue.

Urbanization (especially unplanned), is associated with dengue transmission through multiple social and environmental factors: population density, human mobility, access to a reliable water source, water storage practices, etc.

The community’s risks to dengue also depend on the population’s knowledge, attitude, and practice toward dengue, as well as the implementation of routine sustainable vector control activities in the community. 

Consequently, disease risks may change and shift with climate change in tropical and subtropical areas, and vectors might adapt to new environments and climates.

Preventing Dengue Fever

The best way to prevent the disease is to prevent bites from infected mosquitoes, particularly if you are living in or traveling to a tropical area. This involves protecting yourself and making efforts to keep the mosquito population down. In 2019, the FDA approved a  vaccine called Dengvaxia to help prevent the disease from occurring in adolescents aged 9 to 16 who have already been infected by dengue. But, there currently is no vaccine to prevent the general population from contracting it.

To Protect Yourself:

• Use mosquito repellents, even indoors.
• When outdoors, wear long-sleeved shirts and long pants tucked into socks.
• When indoors, use air conditioning if available.
• Make sure window and door screens are secure and free of holes. If sleeping areas are not screened or air-conditioned, use mosquito nets.
• If you have symptoms of dengue, speak to your doctor.

To reduce the mosquito population, get rid of places where mosquitoes can breed. These include old tires, cans, or flower pots that collect rain. Regularly change the water in outdoor bird baths and pets' water dishes.

If someone in your home gets dengue fever, be especially vigilant about efforts to protect yourself and other family members from mosquitoes. Mosquitoes that bite the infected family member could spread the infection to others in your home.