Rahamat Unissa*, Bobillapati Jyothirmayi, Amrutha Mounica, Lagadapati Tejaswini, Gurram Asha Latha, Gujjula Nishitha, Chette Swati

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Malla Reddy College of Pharmacy, Maisammaguda, Dhulapally, Secunderabad, Telangana, India.

*Corresponding Author E-mail:,,,,



Dengue is a mosquito borne infection caused by dengue virus. It is common in warm, wet areas of the world. Outbreaks occur in the rainy season. It is rare in the United States. It does not spread from person to person. Symptoms include a high fever, headaches, joint and muscle pain, vomiting, and rashes. In some cases, dengue turns into dengue hemorrhagic fever, which causes bleeding from nose, gums, or under the skin. It can also become dengue shock syndrome, which causes massive bleeding and shock. These forms of dengue are life-threatening. There is no specific treatment. Most people with dengue recover within 2 weeks. Until then, drinking lots of fluids, resting and taking non-aspirin fever-reducing medicines might be helpful. People with the more severe forms of dengue usually need to get hospitalized and get fluids. It can be prevented by avoiding going to the areas effected with dengue cases, wearing insect repellent with DEET, wearing clothes covering arms, legs and feet and by closing open doors and windows. Population growth, rapid urbanization, increase in international travel from endemic areas and global warming are playing a major role in disease spread. Measures should be taken to control the aforementioned causes to prevent disease spread and reduce epidemic flare up.


KEYWORDS: Dengue hemorrhagic fever (DHF), Dengue shock syndrome (DSS), Dengue fever, Aedes aegypti (Ae. aegypti)




Dengue has become an important public health concern all over the world since the 1950s1,2. Particularly, the disease is growing most rapidly in tropical and subtropical countries where majority of the world’s population resides and increasing health and economic burden3,4.


Dengue is considered to be the predominant vector-borne disease in terms of the number of human infections occurring globally5.


Received on 24.04.2018                Modified on 25.09.2018

Accepted on 21.01.2018            © A&V Publications All right reserved

Asian J. Res. Pharm. Sci. 2018; 8(4): 192-202.

DOI: 10.5958/2231-5659.2018.00033.4

However, neither vaccines nor specific treatment for DF/DHF are currently available1,6. The disease is caused by four serotypes (viz. DENV-1, DENV-2, DENV-3, and DENV-4) of the genus Flavivirus and transmitted mainly by the mosquito Aedes aegypti (Ae. aegypti) though other species such as Aedes albopictus (Ae. albopictus) can also be vectors of dengue virus transmission7,8.


The symptoms of the disease range from a non-specific febrile illness, muscle and bone pain [as in dengue Fever (DF)] to a more severe illness with bleeding tendency, thrombocytopenia, severe headache and plasma leakage [dengue hemorrhagic fever (DHF)9. In recent decades, DHF has become a major cause of hospitalization and death among children in most of the Asian countries10. Dengue is found mainly in urban and semi-urban areas of the tropical and subtropical regions and people from all income levels (e.g. rich and poor) within the endemic regions suffer from morbidity and mortality of the disease. The incidence of dengue has increased by 30 fold, parallel with increasing dramatically.



Dengue is found in tropical and sub-tropical climates worldwide, mostly in urban and semi-urban areas11. People of all ages who are exposed to infected mosquitoes can get dengue fever. The disease occurs most often during the rainy season in areas with high numbers of infected mosquitoes12. Only infected mosquitoes transmit dengue virus13. The virus is transmitted to humans through the bites of infected female mosquitoes11. The incubation period is 3 to 14 days13. The period of illness is 3–7 days15. A person with dengue fever is not contagious12.


Common names for dengue fever:

Include breakbone fever and dandy fever; dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are the severe forms11.



In many parts of the tropics and subtropics, dengue is endemic, that is, it occurs every year, usually during a season when Aedes mosquito populations are high, often when rainfall is optimal for breeding. These areas are, however, additionally at periodic risk for epidemic dengue, when large numbers of people become infected during a short period. Dengue epidemics require a coincidence of large numbers of vector mosquitoes, large numbers of people with no immunity to one of the four virus types (DENV 1, DENV 2, DENV 3, DENV 4), and the opportunity for contact between the two16,17. Although Aedes are common in the southern U. S., dengue is endemic in northern Mexico, and the U.S. population has no immunity, the lack of dengue transmission in the continental U.S. is primarily because contact between people and the vectors is too infrequent to sustain transmission.


Global Dengue17:

Today about 2.5 billion people, or 40% of the world’s population, live in areas where there is a risk of dengue transmission. Dengue is endemic in at least 100 countries in Asia, the Pacific, the Americas, Africa, and the Caribbean. The World Health Organization (WHO) estimates that 50 to 100 million infections occur yearly, including 500,000 DHF cases and 22,000 deaths, mostly among children.



Dengue virus (DENV) is the cause of dengue fever. It is a mosquito-borne single positive-stranded RNA virus of the family Flaviviridae; genus Flavivirus18,19. Five serotypes of the virus have been found,20,21 all of which can cause the full spectrum of disease18. Nevertheless, scientists are finding their understanding of dengue virus may be simplistic, as rather than distinct antigenic groups there appears to be a continuum22. This same study identified 47 strains of dengue virus23. Additionally, coinfection with and lack of rapid tests for zika virus and chikungunya complicate matters in real world infections.



Figure 1: Global distribution of dengue


Viral Structure18:

Dengue viruses are round in shape and covered in a viral envelope. This envelope comes from the membrane of an infected human cell and is covered with two viral proteins: E and M. These proteins help the virus attach to and infect human skin cells.


Inside of the envelope is the viral genome coated by C protein, which forms a nucleocapsid. The viral genome is a single piece of single-stranded RNA. Instead of making each viral protein separately, this RNA is translated by the host cell to form a polypeptide, or long protein strand. The individual viral proteins are made by cutting up the polypeptide into smaller pieces. This process makes all ten of the viral proteins dengue virus needs to replicate, including the other nonstructural viral protein (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5)24.



Figure 2: Structure of dengue virus



Life cycle:

Until a few hundred years ago, dengue virus was transmitted in sylvatic cycles in Africa and Asia between mosquitoes of the genus Aedes and non-human primates with rare emergences into human populations25. The global spread of dengue virus, however, has followed its emergence from sylvatic cycles and the primary life cycle now exclusively involves transmission between humans and Aedes mosquitoes.26 Vertical transmission from mosquito to mosquito has also been observed in some vector species27.


Recent findings suggest that, as the virus infects human cells, host homeostatic processes like autophagy and ER stress response, not to mention apoptosis, are triggered depending on the infected cell type28. The activation of autophagy and ER stress during infection enhances virus reproduction.29 


Mechanism of Infection30:

1.    Dengue virus’ (DENV) E envelope protein binds to a cellular receptor. The exact nature of the cellular receptor has not been fully elucidated.

2.    DENV undergoes endocytosis. Acidification of the endosome leads to a conformational change of E, exposing a ‘fusion peptide’ sequence that facilitates fusion of the envelope with the endosomal membrane, releasing the virion capsid into the cytoplasm

3.    Uncoating occurs in the cytoplasm

4.    Host translational machinery (ribosomes) translates the (+) ss RNA into a single polypeptide

5.    Cellular and viral proteinases cleave the polypeptide into 10 proteins (E, M, C and 7 non-structural/enzymatic proteins) while embedded on the ER membrane

6.    As soon as functional RNA-dependent RNA polymerase is synthesised RNA replication can commence. Synthesis is asymmetrical, making 10 times more of the positive sense strand than the negative

7.    Assembly occurs on intracellular membranes which bud into the ER (forming the envelope from the ER membrane). Subsequent budding from the ER through the Golgi and into vesicles allows maturation via post-translational modifications e.g. glycosylation and pH transformational rearrangements

8.    Egress occurs via exocytosis


Immune Response to Dengue:

There are four different types of dengue viruses. They are divided into serotypes, which are distinct variations of a virus or bacteria, based on how they are recognized by the immune system. Dengue virus 1 (DEN-1) was first discovered in Japan in the 1940s. The other three viruses, DEN-2, DEN-3, and DEN-4, are closely related to DEN-1, but are not recognized as the same virus by the immune system.

This means if an individual get infected with DEN-3, his immune system will produce antibodies that recognize only DEN-3. These antibodies will protect him from being infected with DEN-3 again. However, if he is later bitten by a mosquito carrying DEN-1, then DEN-3 antibodies won't protect him from getting infected. These antibodies may actually make the disease much more severe than the first time. While this strange phenomenon is not completely understood, scientists think that our immune response may help the virus to spread and lead to more severe symptoms.


The Centers for Disease Control and Prevention (CDC) estimate that 400 million people are infected each year. Dengue fever is rare in the United States (U.S.), but around 100 cases are reported each year, mostly among people traveling from outside the country. Outbreaks have occurred in Texas, Florida, and Hawaii.


Transmission of the Dengue Virus31:

Dengue is transmitted between people by the mosquitoes Aedes aegypti and Aedes albopictus, which are found throughout the world. Insects that transmit disease are vectors. In rare cases dengue can be transmitted in organ transplants or blood transfusions from infected donors, and there is evidence of transmission from an infected pregnant mother to her fetus. But in the vast majority of infections, a mosquito bite is responsible.



Symptoms vary depending on the severity of the disease.

Symptoms can appear up to 7 days after being bitten by the mosquito that carries the virus.

They include:

·      Aching muscles and joints

·      Body rash that can disappear and then reappear

·      High fever

·      Intense headache

·      Pain behind the eyes

·      Vomiting and feeling nauseous


Symptoms usually disappear after a week, and mild dengue rarely involves serious or fatal complications.


Dengue hemorrhagic fever:

At first, symptoms of DHF may be mild, but they gradually worsen within a few days. As well as mild dengue symptoms, there may be signs of internal bleeding.


A person with Dengue hemorrhagic fever may experience:

·      Bleeding from the mouth, gums, or nose

·      Clammy skin

·      Damage to lymph and blood vessels

·      Internal bleeding, which can lead to black vomit and feces, or stools

·      A lower number of platelets in the blood

·      Small blood spots under the skin

·      Weak pulse


Without prompt treatment, DHF can be fatal.

DHF is characterized by a fever that lasts from 2 to 7 days, with general signs and symptoms consistent with dengue fever. When the fever declines, warning signs may develop. This marks the beginning of a 24 to 48 hour period when the smallest blood vessels (capillaries) become excessively permeable (“leaky”), allowing the fluid component to escape from the blood vessels into the peritoneum (causing ascites) and pleural cavity (leading to pleural effusions). This may lead to failure of the circulatory system and shock, and possibly death without prompt, appropriate treatment. In addition, the patient with DHF has a low platelet count and hemorrhagic manifestations, tendency to bruise easily or have other types of skin hemorrhages, bleeding nose or gums, and possibly internal bleeding.


Dengue shock syndrome:

DSS is a severe form of dengue. It can be fatal.

Apart from symptoms of mild dengue fever, the person may experience:

·      Intense stomach pain

·      Disorientation

·      Sudden hypotension, or a fast drop in blood pressure

·      Heavy bleeding

·      Regular vomiting

·      Blood vessels leaking fluid


Without treatment, this can result in death


Figure 3: Picture of Aedes albopictus mosquito



The signs and symptoms of dengue fever are similar to some other diseases, such as typhoid fever and malaria. This can sometimes delay an accurate diagnosis. the doctor will assess the symptoms and the person's medical and travel history, and they may order some blood tests to confirm the diagnosis. Since no protective vaccine or specific treatments are available for dengue fever accurate diagnosis is critical for the early initiation of specific preventive health measures to curtail epidemic spread and reduce economic losses as well as the timely monitoring of patients to prevent fatalities.



Commonly used diagnostic methods for confirming dengue infection involve virus isolation, detection of virus antigen or RNA, and the presence of dengue virus-specific antibodies.


Health care professionals may also use a blood test called the DENV Detect IgM Capture ELISA to diagnose people with dengue fever.



There is no specific medication for treatment of a dengue infection. Persons who think they have dengue should use analgesics (pain relievers) with acetaminophen and avoid those containing ibuprofen, Naproxen, aspirin or aspirin containing drugs. They should also rest, drink plenty of fluids to prevent dehydration, avoid mosquito bites while febrile and consult a physician.


As with dengue, there is no specific medication for DHF. If a clinical diagnosis is made early, a health care provider can effectively treat DHF using fluid replacement therapy. Adequate management of DHF generally requires hospitalization.


Milder forms of dengue can be treated by:

·      Preventing dehydration:

A high fever and vomiting can dehydrate the body. The person should drink clean water, ideally bottled rather than tap water. Rehydration salts can also help replace fluids and minerals.

·      Painkillers, such as Tylenol or paracetamol:

These can help lower fever and ease pain.


·        Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen, are not advised, as they can increase the risk of internal bleeding.


More severe forms of dengue fever may need:

·        Intravenous (IV) fluid supplementation, or drip, if the person cannot take fluids by mouth

·        Blood transfusion, for patients with severe dehydration

·        Hospitalization will allow the individual to be properly monitored, in case symptoms get worse.


Suspected Dengue:

Oral rehydration therapy is recommended for patients with moderate dehydration caused by high fever and vomiting. Patients with known or suspected dengue fever should have their platelet count and hematocrit measured daily from the third day of illness until 1-2 days after defervescence. Patients with clinical signs of dehydration and patients with a rising hematocrit level or falling platelet count should have intravascular volume deficits replaced under close observation. Those who improve can continue to be monitored in an outpatient setting, and those who do not improve should be admitted to the hospital for continued hydration.

Patients who develop signs of dengue hemorrhagic fever warrant closer observation. Admission for intravenous fluid administration is indicated for patients who develop signs of dehydration, such as the following:

·      Tachycardia

·      Prolonged capillary refill time

·      Cool or mottled skin

·      Diminished pulse amplitude

·      Altered mental status

·      Decreased urine output

·      Rising hematocrit

·      Narrowed pulse pressure

·      Hypotension


Severe Dengue:

Successful management of severe dengue requires careful attention to fluid management and proactive treatment of hemorrhage. Admission to an intensive care unit is indicated for patients with dengue shock syndrome.


Patients may need a central intravenous line for volume replacement and an arterial line for accurate blood pressure monitoring and frequent blood tests. Exercise caution when placing intravascular catheters because of the increased bleeding complications of dengue hemorrhagic fever. Urethral catheterization may be useful to strictly monitor urine output.


Intravascular volume deficits should be corrected with isotonic fluids such as Ringer lactate solution. Boluses of 10-20 mL/kg should be given over 20 minutes and may be repeated. If this fails to correct the deficit, the hematocrit value should be determined. If it is rising, limited clinical information suggests that a plasma expander may be administered. Starch, dextran 40, or albumin 5% at a dose of 10-20 mL/kg may be used. One study has suggested that starch may be preferable because of hypersensitivity reactions to dextran. 33


If the patient does not improve after infusion of a plasma expander, blood loss should be considered. Patients with internal or gastrointestinal bleeding may require transfusion, and patients with coagulopathy may require fresh frozen plasma.


After patients with dehydration are stabilized, they usually require intravenous fluids for no more than 24-48 hours. Intravenous fluids should be stopped when the hematocrit falls below 40% and adequate intravascular volume is present. At this time, patients reabsorb extravasated fluid and are at risk for volume overload if intravenous fluids are continued. Do not interpret a falling hematocrit value in a clinically improving patient as a sign of internal bleeding.




Platelet and fresh frozen plasma transfusions may be required to control severe bleeding. A case report demonstrated good improvement following intravenous anti-D globulin administration in 2 patients. The authors proposed that, as in immune thrombocytopenic purpura from disorders other than dengue, intravenous anti-D produces Fcγ receptor blockade to raise platelet counts. 34


Patients who are resuscitated from shock rapidly recover. Patients with dengue hemorrhagic fever or dengue shock syndrome may be discharged from the hospital when they meet the following criteria:

·      Afebrile for 24 hours without antipyretics

·      Good appetite, clinically improved condition

·      Adequate urine output

·      Stable hematocrit level

·      At least 48 hours since recovery from shock

·      No respiratory distress

·      Platelet count greater than 50,000 cells/μL


Pregnant patients:

Dengue in pregnancy must be carefully differentiated from preeclampsia. An overlap of signs and symptoms, including thrombocytopenia, capillary leak, impaired liver function, ascites, and decreased urine output may make this clinically challenging. Pregnant women with dengue fever respond well to the usual therapy of fluids, rest, and antipyretics. However, 3 cases of maternal death due to dengue fever in the third trimester have been reported. An awareness of the clinical and laboratory manifestations of dengue in pregnancy should allow its early recognition and the institution of appropriate treatment. If the mother acquires infection in the peripartum period, newborns should be evaluated for dengue with serial platelet counts and serological studies. 35,36



Ayurvedic Treatment:

Several ayurvedic herbs have been shown to be effective in treatment of dengue fever.


They include:


Amaltas is the root of the cassia tree. It is used as tonic for reducing fever in dengue infection.



Chirayata is very effective for reduction of fevers. It is useful for treating convulsions that occur with fever in dengue.



Datura leaves are effective in reducing the fever in dengue infection. It helps to reduce the seriousness of fever in dengue infection.



Hara dhania:

Coriander leaves taken as tonic can reduce fever in dengue.



Powdered Hermal seeds taken eithers in infusion or as decoction can help to treat intermittent and recurrent fevers in dengue.



An infusion of kanghi can help to reduce fever in dengue.


Giloy ormrita:

It is an anti-inflammatory (that reduces inflammation) and antipyretic (that reduce fever) herb. This herb, which has been used in ayurvedic Rasayanas since centuries, is very helpful in building up the immune system and the body's defense against infecting organisms. In scientific study conducted using human WBC (white blood corpuscles), the ayurvedic herb helps in enhancing the killing ability of macrophages (the resistant cells which are responsible for fighting foreign bodies as wells microorganisms).


Some other herbs that are effective in the treatment of fever in dengue include methi, punarnava, rojmari, tulsi leaves.


Homeopathic Treatment for Dengue39,40:

Since ages, homeopathic treatment has successfully treaded into realms where allopathic medications have failed to provide convincing cures. Homeopathy has also been increasingly favoured by today’s generation because it is free from side effects and negative repercussions. Homeopathic doctors have come up with particular formulation which has been reasonably successful in combating dengue fever. The formulation reads as cRHUS TOX. / EUPATORIUM PERF. / LEDUM PALUSTRE. / GELSEMIUM. / 5CH.



RhusTox is from Poison Ivy. Rhustox is the remedy in Backache, Body aches during flu, Lumbago, Rheumatism, Sprains.



Eupatorium perfoliatum, a common perennial plant relieves pain in limbs and muscles that accompanies some forms of febrile disease, like malaria and influenza. Eupatorium acts principally upon the gastro-hepatic organs and bronchial mucous membrane.


Ledum Palustre:

It is used for muscle and joint pain (rheumatism), cough, bronchitis, cold, cough, and chest and lung ailments. It is also used to stimulate milk flow, cause sweating, increase urine flow to relieve water retention, and loosen phlegm. Some women use marsh tea to cause an abortion.


Diet For Dengue Patient40:

There is no recommendation regarding diet during dengue fever and after dengue fever. Like with any other febrile illness, eat foods which can be easily digested.

·      Patient’s diet can include boiled vegetables, rice gruel, porridge, soup, toast, apples, bananas and tea.

·      Drink plenty of fluids such as oral rehydration solution, fresh juice, soups, and coconut water. This will help to prevent dehydration due to vomiting and high fever. Avoid fried foods and foods with oil, spices and salt.

·      One can use lemon juice or certain herbs to enhance the flavour of their food. according to some experts of ayurveda, tea made with fever reducing herbs such as ginger and cardamom is helpful.

·      Ayurveda recommends having the juice or the extract of two fresh crushed papaya leaves. Take this juice daily. It is considered good home remedy for the treatment of dengue fever.


Diet and Activity:

No specific diet is necessary for patients with dengue fever. Patients who are able to tolerate oral fluids should be encouraged to drink oral rehydration solution, fruit juice, or water to prevent dehydration from fever, lack of oral intake, or vomiting. Return of appetite after dengue hemorrhagic fever or dengue shock syndrome is a sign of recovery.


Bed rest is recommended for patients with symptomatic dengue fever, dengue hemorrhagic fever, or dengue shock syndrome. Permit the patient to gradually resume their previous activities, especially during the long period of convalescence.



The only way to truly prevent dengue virus acquisition is to avoid being bitten by a vector mosquito. Although this can be accomplished by avoiding travel to areas where dengue is endemic, that is not an ideal strategy because it would require a person to avoid most tropical and subtropical regions of the world, many of which are popular travel and work destinations. Other measures are as follows:

·      Wear N, N-diethyl-3-methylbenzamide (DEET)–containing mosquito repellant

·      Wear protective clothing, preferably impregnated with permethrin insecticide

·      Remain in well-screened or air-conditioned places

·      The use of mosquito netting is of limited benefit, as Aedes are day-biting mosquitoes

·      Eliminate the mosquito vector using indoor sprays


The most widely used mosquito-control technique, spraying cities to kill adult mosquitoes, is not effective. Efforts should target the larval phase with larvicides and cleaning up larvae habitats. Poor sanitation and poor refuse control provide excellent conditions for mosquito larvae to grow. Hurricanes and other natural disasters increase the habitat for mosquito growth in urban areas by increasing rubble and garbage, which act as water reservoirs.


Breeding of vector mosquitoes can be reduced by eliminating small accumulations of stagnant water around human habitats (eg, disposing of old tires, covering water receptacles, and changing water in birdbaths daily. Support community-based vector control programs (including source reduction) and the use of vectoricidal agents, including predatory copepods as biological control agents. [41,42,43,44]




Figure 4: Breeding places of mosquitos



Figure 5: Potential breeding places of  the mosquitos


In 2011, an Australian research effort infected Aedes aegypti mosquitoes with the intracellular bacterium Wolbachia in the laboratory. Maternally inherited Wolbachia prevents dengue virus from replicating within mosquitos. They then released these mosquitos into the wild to mate with wild mosquitos and pass the Wolbachia along to their offspring. After releasing approximately 10 mosquitos/house/week for 10 weeks, they found that greater than 80% of collected wild mosquitos had Wolbachia infection. Infected mosquitos laid fewer eggs and exhibited shorter life spans. The research group plans further field trials in Vietnam, Indonesia, and Brazil. If successful, this would provide a practical biological approach to dengue suppression. 45

Outbreaks of dengue will increasingly cross common borders of endemic and disease-free countries unless the following measures are undertaken:

·      Increased health surveillance

·      Prompt reporting of new cases

·      Heightened professional awareness

·      Public education


General preventive measures:

No vaccine can protect against dengue fever. Only avoiding mosquito bites can prevent it.


Anyone who lives in or travels to an at-risk area can use a number of ways to avoid being bitten.



Reduce the amount of skin exposed by wearing long pants, long-sleeved shirts, and socks, tucking pant legs into shoes or socks, and wearing a hat


Mosquito repellents:

Use a repellent with at least 10 percent concentration of diethyltoluamide (DEET), or a higher concentration for longer lengths of exposure. Avoid using DEET on young children.


Mosquito traps and nets:

Nets treated with insecticide are more effective, otherwise the mosquito can bite through the net if the person is standing next to it. The insecticide will kill mosquitoes and other insects, and it will repel insects from entering the room.


Door and window screens:

Structural barriers, such as screens or netting, can keep mosquitos out.


Avoid scents:

Heavily scented soaps and perfumes may attract mosquitos.


Camping gear:

Treat clothes, shoes, and camping gear with permethrin, or purchase clothes that have been pretreated.


Try to avoid being outside at dawn, dusk, and early evening.


Stagnant water:

The Aedes mosquito breeds in clean, stagnant water. Checking for and removing stagnant water can help reduce the risk.


To reduce the risk of mosquitoes breeding in stagnant water:

·        Turn buckets and watering cans over and store them under shelter so that water cannot accumulate

·        Remove excess water from plant pot plates

·        Scrub containers to remove mosquito eggs

·        Loosen soil from potted plants, to prevent puddles forming on the surface

·        Make sure scupper drains are not blocked and do not place potted plants and other objects over them

·        Use non-perforated gully traps, install anti-mosquito valves, and cover any traps that are rarely used

·        Do not place receptacles under an air-conditioning unit

·        Change the water in flower vases every second day and scrub and rinse the inside of the vase

·        Prevent leaves from blocking anything that may result in the accumulation of puddles or stagnant water

·        When camping or picnicking, choose an area that is away from still water.



Figure 6 : Preventive measures


Vaccine Development:

One vaccine is currently approved for the prevention of dengue infection. Sanofi Pasteur registered Dengvaxia (CYD-TDV), a live recombinant tetravalent vaccine, in several countries in late 2015-2016, with Mexico being the initial country to register the vaccine in December 2015 The vaccine is given in 3 doses at age 0, 6, and 12 months. It underwent testing in more than 30,000 volunteers and was shown to reduce the risk of severe illness and hospitalization by as much as 30% in individuals previously infected with one or more strains. The vaccine proved less effective in persons who were not previously exposed to dengue and in areas with a lower burden of disease. 46,47 Owing to concern that the vaccine may act like an initial dengue infection in this second group of individuals not previously infected with the virus, with additional exposure to a second serotype placing these individuals at increased risk of severe dengue, the WHO released a position paper in July 2016, stating that countries should consider introduction of vaccine as a part of an comprehensive dengue control strategy only where epidemiologic data indicate a high burden of disease. 48


Dengue vaccine development was prolonged because immunity to a single dengue strain is the major risk factor for severe dengue; as such, a vaccine must provide high levels of immunity to all 4 dengue strains to be clinically useful. 49Seroconversion alone does not predict protection. Several other immunogenic tetravalent vaccine candidates have been developed and are undergoing clinical trials. 50,51,52,53



Consultation with an infectious diseases specialist may be helpful in guiding decisions regarding diagnosis and treatment. Consultation with a critical care medicine specialist may be helpful when treating patients with dengue hemorrhagic fever or dengue shock syndrome and severe hemorrhagic manifestations or shock.


Telephone consultation may be obtained from the Centers for Disease Control and Surveillance (800-232-4636, 8am-8pm ET/Monday-Friday).


Fast facts on dengue fever:

Here are some key points about dengue fever. More detail is in the main article.

·        Dengue is a mosquito-borne viral infection.

·        It is transmitted by the mosquitoes Aedes aegypti and Aedes albopictus, which are found throughout the world.

·        Around 2.5 billion people, or 40 percent of the world's population, live in areas where there is a risk of dengue transmission.

·        Dengue is endemic in at least 100 countries in Asia, the Pacific, the Americas, Africa, and the Caribbean.

·        Symptoms usually begin 4 to 7 days after the mosquito bite and typically last 3 to 10 days.

·        The infection causes flu-like illness, and occasionally develops into a potentially lethal complication called severe dengue.

·        Effective treatment is possible if a clinical diagnosis is made early.

·        There is no specific treatment for dengue/ severe dengue, but early detection and access to proper medical care lowers fatality rates below 1%.

·        Dengue prevention and control depends on effective vector control measures.

·        A dengue vaccine has been licensed by several National Regulatory Authorities for use in people 9-45 years of age living in endemic settings.


WHO response:

WHO responds to dengue in the following ways:

·        supports countries in the confirmation of outbreaks through its collaborating network of laboratories;

·        provides technical support and guidance to countries for the effective management of dengue outbreaks;

·        supports countries to improve their reporting systems and capture the true burden of the disease;

·        provides training on clinical management, diagnosis and vector control at the regional level with some of its collaborating centres;

·        formulates evidence-based strategies and policies;

·        develops new tools, including insecticide products and application technologies;

·        gathers official records of dengue and severe dengue from over 100 Member States; and

·        Publishes guidelines and handbooks for case management, diagnosis, dengue prevention and control for Member States.



A poster in Tampines, Singapore, notifying people that there are 10 or more cases of dengue in the neighborhood (November 2015).

International Anti-Dengue Day is observed every year on 15 June.54 The idea was first agreed upon in 2010 with the first event held in Jakarta, Indonesia in 2011.Further events were held in 2012 in Yangon, Myanmar and in 2013 in Vietnam.54 Goals are to increase public awareness about dengue, mobilize resources for its prevention and control and, to demonstrate the Asian region's commitment in tackling the disease.55



Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute:

Rao Saheb Achutrao Patwardhan Marg,

Four Bunglows,

Andheri (W)-400052

Phone: 022 30999999


Seven Hills Hospitals:

Seven Hills Health City,

MarolMaroshi Road,

Andheri East,

Mumbai – 400059

Ph: 022-67676767


Indraprasth Apollo Hospitals:

Sarita Vihar

Delhi Mathura Road,

New Delhi - 110076

Tel.: + (91)-11-26925858 / 26925801


CIMET's Inamdar Multispeciality Hospital:

Hospital Building S. No, 15, Fatima Nagar, Pune

Maharashtra 411 040, India

+91 - 020 – 66812288



P.B.No.1, Nayara P.O

Trivandrum - 695 029, Kerala, India

+91 471 3041000, +91 471 2447575


Fortis Escorts Hospital:

Jawaharlal Nehru Marg, Malviya Nagar,

Jaipur - 302017,


Phone: +91 141 254 7000, +91 141 409 7109



Dengue is one of the major public health problems which can be controlled with active participation of the community, health care industries and governing bodies. Though government and the pharmaceutical industries are also taking initiative to develop new strategies to improve the diagnosis and treatment of dengue. The challenge here lies in how effectively the strategies developed are put into use.Need is to organize health education programmes about dengue disease to increase community knowledge and sensitize the community to participate in integrated vector control programmes. Combined efforts of the health care industries, governing bodies and efforts at individual level would help us to tackle the prevalence of dengue.



·        DHF : Dengue hemorrhagic fever

·        DSS : Dengue shock syndrome

·        DEET : N,N-diethyl-3-methylbenzamide

·        CDC : Centers for Disease Control and Prevention

·        NSAIDs : Non-steroidal anti-inflammatory drugs,

·        WHO : World Health Organization (WHO)



1.     Alexander N, Balmaseda A, Coelho ICB, Dimaano E, Hien TT, Hung NT, et al. Multicentre prospective study on dengue classification in four South-east Asian and three Latin American countries. Trop Med Int Health 2011; 16: 936-948.

2.     Guzman MG. Dengue vaccines: new developments. Drugs Future 2011; 36: 45-62.

3.     Toledo ME, Rodrigues A, Valdes L, Carrion R, Cabrera G, Banderas D, et al. Evidence on impact of community-based environmental management on dengue transmission in Santiago de Cuba. Trop Med Int Health 2011; 16: 744-747.

4.     Suaya JA, Shepard DS, Beatty ME. Dengue: Burden of disease and costs of illness. Working Paper 3.2. Geneva, Switzerland: World Health Organization; 2006.

5.     National Research Council. Under the weather: climate, ecosystems and infectious disease. Washington, D.C.: National Academy Press; 2001.

6.     World Health Organization. Dengue: guidelines for diagnosis, treatment, prevention and control. Geneva, Switzerland: World Health Organization; 2009.

7.     San Martin JL, Brathwaite O, Zambrano B, Solorzano JO, Bouckenooghe A, Dayan GH, et al. The epidemiology of dengue in the americas over the last three decades: A worrisome reality. Am J Trop Med Hyg 2010; 82: 128-135.

8.     Halstead SB. Dengue fever/dengue hemorrhagic fever. In: Cohen J, Powderly WG, editors. Infectious Diseases. Vol.2, 2nd ed. Spain: Mosby; 2004, p. 1681-1689.

9.     Potts JA, Rothman AL. Clinical and laboratory features that distinguish dengue from other febrile illnesses in endemic populations. Trop Med Int Health 2008; 13: 1328-1340.

10.   World Health Organization. Dengue and dengue haemorrhagic fever. Fact Sheet No. 117. Geneva, Switzerland: World Health Organization; 2009.

11.   Wiatrek, Melissa. Dengue Fever.

12.   World Health Oraganization. Dengue and severe dengue. April 2017.

13.   District of Columbia department of health. Dengue Fever Factsheet.

14.   BetterHealth.Denguevirusdisease.

15.   Centers for Disease Control and Prevention. Epidemiology.

16.   WHO TDR Global Alert and Repsonse Dengue/Dengue Haemorrhagic Fever [webpage on the Internet] Geneva: World Health Organization (WHO); March,2013. Wilder-Smith A, Ooi EE, Vasudevan SG, Gubler DJ. Update on dengue: epidemiology, virus evolution, antiviral drugs, and vaccine development. Curr Infect Dis Rep. 2010;12(3):157–164

17.   Rodenhuis-Zybert, Izabela A.; Wilschut, Jan; Smit, Jolanda M. "Dengue virus life cycle: viral and host factors modulating infectivity". Cellular and Molecular Life Sciences. 2010;67(16): 2773–2786.

18.   WHO. Dengue Guidelines for Diagnosis, Treatment, Prevention and Control (PDF). World Health Organization.2009; ISBN 92-4-154787-1.

19.   Normile, D (October 2013). "Tropical medicine. Surprising new dengue virus throws a spanner in disease control efforts". Science. 342 (6157): 415. Bibcode: 2013Sci.342. 415N.

20.   Dwivedi, V. D., Tripathi, I. P., Tripathi, R. C., Bharadwaj, S., & Mishra, S. K. Genomics, proteomics and evolution of dengue virus. Briefings in functional genomics.2017;16(4): 217–227,

21.   "A new understanding of dengue virus". ScienceDaily. September 18, 2015. Retrieved May 7, 2016.

22.   "A Second Time Dengue Infection Can be Life-Threatening Says Research". NDTV. United Kingdom. September 18, 2015. Retrieved 2016-05-07.

23.   Hanley, K.A.; Weaver, S.C., eds. Frontiers in Dengue Virus Research. Caister Academic. 2010; ISBN 978-1-904455-50-9.

24.   "Dengue virus". Pathogen Information (PathInfo). Virginia Bioinformatics Institute, Virginia Tech. Archived from the originalon 2010-08-30.

25.   Halstead, SB (1988). "Pathogenesis of dengue: challenges to molecular biology". Science. 1988; 239 (4839): 476–481. 

26.   Haddow, AD; Guzman, H; Popov, VL; Wood, TG; Widen, SG; Haddow, AD; Tesh, RB; Weaver, SC. "First isolation of Aedes flavivirus in the Western Hemisphere and evidence of vertical transmission in the mosquito Aedes (Stegomyia) albopictus (Diptera: Culicidae)". Virology. 2013;440 (2): 134–9.

27.   Ghosh Roy S, Sadigh B, Datan E, Lockshin RA, Zakeri Z. "Regulation of cell survival and death during Flavivirus infections". World Journal of Biological Chemistry. 2014;5 (2): 93–105.

28.   Datan E, Roy SG, Germain G, Zali N, McLean JE, Harbajan S, Lockshin RA, Zakeri Z (2016). "Dengue-induced autophagy, virus replication and protection from cell death require ER stress (PERK) pathway activation". Cell Death and Disease. 7 (e2127).

29.   Acheson, Nicholas H. (2011). Fundamentals of Molecular Virology, 2nd ed. Wiley.

30.   WHO. Dengue haemorrhagic fever: diagnosis, treatment, prevention and control. World Health Organization. 1997. Available at

31.   Kameel Mungrue. The laboratory diagnosis of dengue virus infection, a review. Adv Lab Med Int. 2014; 4(1): 1-8

32.   Wills BA, Nguyen MD, Ha TL, Dong TH, Tran TN, Le TT, et al. Comparison of three fluid solutions for resuscitation in dengue shock syndrome. N Engl J Med. 2005 Sep 1. 353(9):877-89. 

33.   Yadav SP, Sachdeva A, Gupta D, Sharma SD, Kharya G. Control of massive bleeding in dengue hemorrhagic fever with severe thrombocytopenia by use of intravenous anti-D globulin. Pediatr Blood Cancer. 2008 Dec. 51(6):812-3.

34.   Waduge R, Malavige GN, Pradeepan M, Wijeyaratne CN, Fernando S, Seneviratne SL. Dengue infections during pregnancy: a case series from Sri Lanka and review of the literature. J Clin Virol. 2006 Sep. 37(1):27-33.

35.   Ismail NA, Kampan N, Mahdy ZA, Jamil MA, Razi ZR. Dengue in pregnancy. Southeast Asian J Trop Med Public Health. 2006 Jul. 37(4):681-3.  

36.   Yin Z, Chen YL, Schul W etl.ndenosine nucleoside inhibitor of dengue virus. Proc. NatlAcadSci USA. 2009;106:20435–20439.

37.   World Health Organization. Clinical diagnosis. In: Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control.WHO: Geneva, 1997(2):12–23

38.   William Boericke, Homoeopathic Materia MEDICA,, 10th December 2013

39.   Pratima Sharma. Homeopathic Treatment for Dengue. Only My Health.15th July 2011.Web.26th July 26, 2013

40.   Billingsley PF, Foy B, Rasgon JL. Mosquitocidal vaccines: a neglected addition to malaria and dengue control strategies. Trends Parasitol. 2008 Sep. 24(9):396-400.   

41.   Erlanger TE, Keiser J, Utzinger J. Effect of dengue vector control interventions on entomological parameters in developing countries: a systematic review and meta-analysis. Med Vet Entomol. 2008 Sep. 22(3):203-21. 

42.   Kay B, Vu SN. New strategy against Aedes aegypti in Vietnam. Lancet. 2005 Feb 12-18. 365(9459):613-7. 

43.   Hanh TT, Hill PS, Kay BH, Quy TM. Development of a framework for evaluating the sustainability of community-based dengue control projects. Am J Trop Med Hyg. 2009 Feb. 80(2):312-8. 

44.   Hoffmann AA, Montgomery BL, Popovici J, Iturbe-Ormaetxe I, Johnson PH, Muzzi F, et al. Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission. Nature. 2011 Aug 24. 476 (7361):454-7.

45.   Sanofi Pasteur and International Vaccine Institute Partner Against Dengue. Available at Accessed: October 20, 2011.

46.   Lang J. Recent progress on sanofi pasteur's dengue vaccine candidate. J Clin Virol. 2009 Oct. 46 Suppl 2:S20-4. 

47.   World Health Organization. Dengue vaccine: WHO position paper – July 2016. Wkly Epidemiol Rec. 2016 Jul 29. 91 (30):349-64. 

48.   Monath TP. Dengue and yellow fever--challenges for the development and use of vaccines. N Engl J Med. 2007 Nov 29. 357(22):2222-5. 

49.   McArthur JH, Durbin AP, Marron JA, Wanionek KA, Thumar B, Pierro DJ, et al. Phase I clinical evaluation of rDEN4Delta30-200,201: a live attenuated dengue 4 vaccine candidate designed for decreased hepatotoxicity. Am J Trop Med Hyg. 2008 Nov. 79(5):678-84. 

50.   O'Brien J. 12th Annual Conference on Vaccine Research. Expert Rev Vaccines. 2009 Sep. 8(9):1139-42. 

51.   Edelman R. Dengue vaccines approach the finish line. Clin Infect Dis. 2007 Jul 15. 45 Suppl 1:S56-60.

52.   Blaney JE Jr, Durbin AP, Murphy BR, Whitehead SS. Development of a live attenuated dengue virus vaccine using reverse genetics. Viral Immunol. 2006 Spring. 19(1):10-32.

53.   "Marking ASEAN Dengue Day". Archived from the original on 17 June 2015. Retrieved 16 June 2015.

54.   Action Against Dengue Dengue Day Campaigns Across Asia. World Health Organization. 2011.







Received on 17.07.2018                Modified on 27.09.2018

Accepted on 25.10.2018            © A&V Publications All right reserved

Asian J. Res. Pharm. Sci. 2018; 8(4): 185-191.

DOI: 10.5958/2231-5659.2018.00032.2