Dengue

Dengue is a mosquito-borne viral disease –widely distributed in tropics/sub-tropics

• Dengue word from Swahili, Ki denga pepo=sudden seizure by demon
• Also called “break-bone fever”, term coined during Philadelphia epidemic in 1780
• Dengue is clinically similar to Chikun Gunya
• Dengue virus is transmitted by female mosquitoes mainly of the species Aedes aegypti and, to a lesser extent, Ae. albopictus. These mosquitoes are also vectors of chikungunya, yellow fever and Zika viruses. 
• Dengue causes a subclinical disease (people may not know they are even infected) to severe flu-like symptoms in those infected. Some people develop severe dengue, with severe bleeding, organ impairment and/or plasma leakage-with higher risk of death when not managed appropriately.
• Severe dengue was first recognized in the 1950s during dengue epidemics in the Philippines and Thailand. Today, severe dengue affects most Asian and Latin American countries and has become a leading cause of hospitalization and death among children and adults in these regions.

 Dengue Virus

• Dengue is caused by a virus of the Flaviviridae family - four distinct, but closely related, serotypes of the virus -DENV-1, DENV-2, DENV-3 and DENV-4.
• RNA virus
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• Recovery from infection is believed to provide lifelong immunity against that serotype- immunity is type specific
• That means, One can have four separate episodes of Dengue
• Subsequent infections (secondary infection) by other serotypes increase the risk of developing severe dengue. 

Epidemiology

• Dengue is found in tropical and sub-tropical climates worldwide, mostly in urban and semi-urban areas.
• Dengue is the most important vector borne disease in the world, with 2.3 billion people in around 200 countries at risk
• About half of the world's population is now at risk. There are an estimated 100-400 million infections each year.
• Many countries are hyper-endemic for all four serotypes.
• 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. 
• 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 travellers-when susceptible vectors are present in these new areas, local transmission is established.

Transmission

Mosquito to Human transmission- 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.

• Once infectious, the mosquito is capable of transmitting virus for the rest of its life (~1-2 months)
• Ae. aegypti is a day-time feeder; its peak biting periods are early in the morning and in the evening before sunset -. It lives in urban habitats and breeds mostly in man-made containers
• After feeding on an 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)-about 8-12 days when the ambient temperature is between 25-28°C.
• Variations in the extrinsic incubation period are influenced by temperature, virus genotype, initial viral concentration 

Human-to-mosquito transmission

• Mosquitoes can become infected from people who are viremic with DENV- symptomatic, pre-symptomatic (yet to have a symptomatic infection and also asymptomatic (no signs of illness)
• 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 
• Risk of mosquito infection is positively associated with high viremia and high fever in the patient
• Most people are viremic for about 4-5 days, but viremia can last as long as 12 days.

 Other modes of transmission

• The primary mode of transmission of DENV between humans involves mosquito vectors
• Possibility of maternal transmission (from a pregnant mother to her baby) during the pregnancy -when a mother has DENV infection when she is pregnant, babies may suffer from pre-term birth, low birthweight, and fetal distress  

Signs and symptoms

• Dengue is a severe, flu-like illness that affects infants, young children and adults, but seldom causes death.
• After an incubation period of 4–10 days following the bite from an infected mosquito,  symptoms appear and last for 2–7 days, 
• Dengue should be suspected when a high fever (40°C) is accompanied by 2 of the following symptoms during the febrile phase:

·         severe headache

·         pain behind the eyes

·         muscle and joint pains-  Pain in the back and limbs (break bone fever)

·         Lymphadenopathy

·         rash 

·         nausea

·         vomiting

 Severe dengue

• About 3-7 days after illness onset, a patient enters  the critical phase 
• The fever is dropping (below 38°C) in the patient, but warning signs associated with severe dengue can manifest. Severe dengue is a potentially fatal complication, due to plasma leaking, fluid accumulation, respiratory distress, severe bleeding, or organ impairment.
• Proper medical care should be provided, to avoid complications and risk of death.

Dengue can occur with hemorrhagic symptoms (Dengue hemorrhagic fever) or with shock (dengue shock syndrome)- hypersensitivity or enhanced immune response to subsequent dengue infection in people sensitized by prior exposure to other serotypes of the virus

 Diagnostics

• virological tests (that directly detect elements of the virus) & serological tests, which detect antibodies produced in response to the virus).
• Patient samples collected during the first week of illness should be tested by both serological (ELISA) and virological methods (RT-PCR).

Serological methods

• Enzyme-linked immunosorbent assays (ELISA) to confirm the presence of a recent or past infection, with the detection of IgM and IgG anti-dengue antibodies.
•  IgM antibodies are detectable ~1 week after infection and are highest at 2 to 4 weeks after the onset of illness. They remain detectable for about 3 months. The presence of IgM is indicative of a recent DENV infection.
• IgG antibody levels take longer to develop than IgM, but IgG remain in the body for years. The presence of IgG is indicative of a past infection.

Virological methods

• The virus may be isolated from the blood during the first few days of infection by reverse transcriptase–polymerase chain reaction (RT–PCR) methods
• RT–PCR assays are sensitive, but they require specialised equipment and technical training for staff implementing the test, therefore they are not always available in all medical facilities.
• RT–PCR products from clinical samples may also be used for genotyping of the virus, allowing comparisons with virus samples from various geographical sources.

Treatment

• There is no specific treatment for dengue fever.
• Fever reducers and pain killers can be taken to control the symptoms of muscle aches and pains, and fever-acetaminophen or paracetamol.
• NSAIDs (non-steroidal anti-inflammatory drugs), such as ibuprofen and aspirin should be avoided. These anti-inflammatory drugs act by thinning the blood, and in a disease with risk of hemorrhage, blood thinners may worsen the bleeding (no blood clotting)
• For severe dengue, medical care by physicians and nurses experienced with the effects and progression of the disease can save lives – decreasing mortality rates from more than 20% to less than 1%.
• Adequate fluid intake to be ensured. 

Vaccination against dengue

• No vaccine for immunity purpose
• Other disease preventive measures such as well-executed and sustained vector control.
• Individuals, whether vaccinated or not, should seek prompt medical care if dengue-like symptoms occur.
• The first dengue vaccine, Dengvaxia® (CYD-TDV) - for persons living in endemic areas, ranging from 9-45 years of age, who have had at least 1 documented dengue virus infection previously. 
• Vaccine is safe in persons who have had a previous dengue virus infection (seropositive individuals). 
• However, it carries an increased risk of severe dengue in those who experience their first natural dengue infection after vaccination (those who were seronegative at the time of vaccination).

Prevention and control

• Patients with dengue should avoid getting further mosquito bites during the first week of illness. Virus may be circulating in the blood during this time, and therefore may get transmitted to new uninfected mosquitoes, which in turn infect other people.

•  Mosquito vectors controlled through:

• Prevention of mosquito breeding:
• Preventing mosquitoes from accessing egg-laying habitats by environmental management and modification;
• Disposing of solid waste properly and removing artificial man-made habitats that can hold water;
• Covering, emptying and cleaning of domestic water storage containers on a weekly basis;
• Applying appropriate insecticides to water storage outdoor containers;

• Personal protection from mosquito bites:
• Using of personal household protection measures, such as window screens, repellents, insecticide treated materials, coils and vaporizers. These measures must be observed during the day both inside and outside of the home (e.g.: at work/school) because the primary mosquito vectors bites throughout the day;
• Wearing clothing that minimises skin exposure to mosquitoes is advised;

• Community engagement:
• Educating the community on the risks of mosquito-borne diseases;
• Engaging with the community to improve participation for sustained vector control;

• Reactive vector control:
• Emergency vector control measures such as applying insecticides as space spraying during outbreaks may be used by health authorities;

• Active mosquito and virus surveillance:
• Active monitoring and surveillance of vector abundance and species composition should be carried out to determine effectiveness of control interventions;
• Prospectively monitor prevalence of virus in the mosquito population, with active screening of sentinel mosquito collections;