Dengue
P.K.Ghatak, MD.
Dengue Fever.
Dengue fever is a viral illness transmitted by a mosquito bite. The virus belongs to Flaviviridae, genus Flavivirus. The Dengue virus is spherical, the center of the virus is made up of the viral genome and C-protein. The virus acquires a lipid envelope from its victim. The virus was identified in 1943, by Ren Kimra and Susumu Hotts from the blood samples collected during a Dengue epidemic in Nagasaki, Japan.
The virus is a single-stranded positive-sense RNA virus and has 10,700 base pairs. Dengue virus mutates often in endemics and is known as DENV-1, DENV-2, DENV-3, and DENV-4. At a given time, all 4 variants may be circulating in a given location.
Where Dengue is most prevalent:
Febrile illness transmitted by mosquito is recorded since 1600, and was called Dengue but no serological tests were known at that time. Today, it appears that the so-called Dengue is actually a collection of vector borne viral illnesses and one of them is dengue.
Dengue is presently endemic in India, and other South Indian Nations, South China, Taiwan, Pacific Islands, Caribbean, Mexico, Africa, and South and Central America. Dengue virus infects 390 million people and causes 25,000 deaths each year.
How Dengue spreads:
Two closely related mosquito species – Aedes aegypti and Aedes albopictus acquire the virus by biting Dengue patients and then spread the virus to new victims. Other uncommon sources are - the pregnant mother can transmit dengue to her unborn child, infected organ transplantation and blood transfusions. The Dengue virus does not spread from person to person.
What other virus illnesses are spread by Aedes mosquito:
Zika virus.
Yellow fever.
West Nile fever
Chikungunya.
Previous endemics:
Many epidemics and endemics can be traced by looking into the CDC reports but confirmed endemics are as follows-
In 2023, major urban centers of India have seen widespread dengue fever following monsoon floods.
In 2014, Brownsville, Texas, Key West, Florida, and Hawaii experienced Dengue fever.
CDC reports 2,000 cases of dengue in the USA and its territories in 2022..
In 1942, Nagasaki, Japan.
During 2014 to 2016, Singapore recorded 33,000 cases of dengue. A biological method was used to control the endemic and the incidence dropped to 1/3 in 2017 by releasing male Aedes aegypti mosquito infected with bacteria Wolbachia. These bacteria made male mosquitoes sterile and as a result, the mosquito population dropped, and so the incidence of dengue.
Clinical feature:
Incubation period:
3 to 10 days, from the time of the mosquito bites to the onset of fever.
Symptoms:
Abrupt onset of fever, headaches, retro orbital pain, body pain, bone pain, petechia, hematuria, hemorrhage in gastrointestinal tract and brain, prostration and some incidence of deaths.
Clinical types:
Minor fever and bone pain. Most of the patients belong to this group. The fever lasts 2 to 7 days and the fever may be biphasic. In the minority of patients, the symptoms are: high temperature to 104F, severe headaches, retro-orbital pain, muscular and bone pain, ecchymosis, bleeding from gums, epistaxis, hematuria, petechia and abdominal pain.
Weakness, prostration and severe bone pain and severe hemorrhagic episodes called Dengue Hemorrhagic Fever.
Dengue shock syndrome consists of hypotension, shock, and bleeding.
Special aspect of decreased Platelet count:
Low platelet count, usually around 150,000/mL, is seen in most patients and develops on the 3rd and 4th day. On about 7 to 10 days, the platelet numbers return to normal. In 10 to 20 % cases the platelet number falls below 50,000 and may reach a low 20,000/mL. Only about 5% of patients require platelet transfusions. One unit of platelet requires 4 units of blood.
What causes low Platelets:
Multiple processes of low platelet count are identified.
Dengue virus infects various cell types including immune cells - monocytes, macrophages, dendritic cells, and Langerhans cells. Immune cells fail to swallow the virus, generate antibodies, fail to generate killer cells, limit the spread of the virus, and fail to activate anti-inflammatory processes.
Depression of megakaryocytes in the bone marrow.
Destruction of platelets is associated with activation of complement factor C3, and C5 binding to platelets. The DENV-2 alters platelets and activates macrophages to phagocytize platelets.
Dengue antigen, when attached to platelet IgM and IgG, becomes antigenic and starts producing antibodies that cause destruction of platelets.
Diagnostic tests:
Blood test detects Dengue NS1 antigen and also IgM and IgG antibodies. Test kits are commercially available and marketed by the SD Bioline Dengue Duo test. NS1 antigen can be detected early in the stage of the illness. This test is moderately high sensitivity and very high specificity. After 10 days following infection, the serology becomes positive. IgG antibody remains positive 10 months following infection.
Treatment:
In more mild to moderate cases, proper hydration is maintained. For fever and pain in bones and muscles, Acetaminophen is used. Aspirin, NSAID (non-steroidal anti-inflammatory drugs) are contraindicated because those drugs can aggravate bleeding.
Those who develop a low platelet count require close monitoring of the platelet count and boost platelets by platelet transfusions, which may have to be repeated.
“ The Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen) announced, on October 2023, promising data from a Phase 2a human challenge study evaluating JNJ-1802, a first-in-class oral antiviral in development for the prevention of dengue. The data showed that the compound induced antiviral activity against dengue (DENV-3) in humans, compared to placebo, and is safe and well-tolerated. The data were announced at the American Society of Tropical Medicine & Hygiene Annual Meeting in Chicago, Illinois.
Other measures:
To reduce the infection carried by mosquitoes to others, the febrile patients should avoid mosquito bites. Use of these limits mosquito bites – mosquito repellents, wear long-sleeved shirts and long pants and socks. Switch on the air conditioning unit. Covers windows and doors with mosquito nets.
In India, Papaya fruit and extract of Papaya leaves or leaves boiled in water prove to be a reliable platelet booster. In some other Asian countries, Pumpkin is found to spike platelets just like papaya.
Vaccine:
Dengvaxia is the name of a vaccine approved by the FDA for teenagers 9 to 16 years old to prevent recurrence of dengue infection. Serological evidence must be present before the vaccine is administered, otherwise dengue, if contracted, would be much worse. No vaccine for adults is successful so far.
Why dengue vaccines are difficult to make:
The dengue virus stops the immune reactions and inactivates and destroys immune cells that produce antibodies. In an endemic area, more than one variety of dengue virus is active, and dengue virus subtypes 1 to 4, each one has a different antigen. Even a successful vaccine against one subtype will not protect every person
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