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Dengue is a mosquito borne infection (Aedes aegypti), in the recent decades it has become a major international public health concern.
Dengue is found in tropical and sub-tropical regions around the world, predominantly in urban and semi-urban areas.
Few dengue patients can present with concomitant malarial (vivax / falciparum or both) infection.
The disease can be seen equally in male and females.
The first case of dengue hemorrhagic fever was reported in the year 1994. In 2006 Dengue outbreak occurred in Karachi city. In 2010 the largest epidemicof dengue infection was seen throughout Pakistan after heavy rainfall and flood.
Male to Female ratio was a bit high in Pakistan i.e. 1.5:1 (year 2006).
There are 4 serotypes of single stranded RNA virus i.e. DEN 1, DEN 2, DEN 3 and DEN 4. Serotype 4 is associated with mild illness. More than one serotype can circulate at one time. In Pakistan serotype 3 was the first to be reported.
Mostly female Aedes aegypti mosquito causes an outbreak, which feeds on humans during early morning and at sun set time. This mosquito is also called the tiger mosquito.
Very rarely female Aedes albopictus can cause an outbreak, like in South America.
Dengue mosquito breeds in uncovered clean stored water. The favored breeding places are buckets, drums, jars, pots, tanks or places where rainwater can be stored, (even one ml of stored water can be the breeding site). Plants like palm trees or any plant with axils capable of trapping water are the potential breeding sites. The mosquito eggs can become adult mosquito in about 10 days.
Infected humans (already having dengue infection) are the main carriers and multipliers of the dengue virus, serving as a source of virus for the uninfected mosquitoes. Female Aedes aegypti mosquito generally ingests the dengue virus into its body while feedingthe blood of an infected person, mosquito then bites a normal person and ingests the dengue virus into his/her body, this virus usually circulates in the blood of infected humans for two to seven days.
Outbreak occurs in the rainy season or just after rainy season. Vertical transmission (from mother to baby) can also occur, however transmission after needle stick injuries is rare.
Incubation time from mosquito’s bite ranges between 3 and 14 days.
Life span of Aedes aegypti mosquito is usually 21 days, although life span depend on temperature (survives at temperature between 18 to 30 degree Celcius).
A number of mechanisms including antibody dependent enhancement, viral serotype variation, abnormal immune activation and autoimmunity have been implicated in the pathogenesis of Dengue Hemorrhagic Fever (DHF) / Dengue Shock Syndrome (DSS).
(A) After exposure to dengue virus, antibodies are formed against dengue virus non-structural protein 1 (NS1) which cross react with the vascular endothelial cells and cause vascular leakage (bleeding) and result in clinical illness in DHF / DSS.
(B) Hemorrhagic shock syndrome is due to the production of large amount of cross reacting antibodies at the time of second infection. When the patient is infected with another serotype of dengue virus an anamnestic (secondary exposure of the virus causing an increased production of antibodies) response occurs and large amount of cross reacting antibodies to the first serotype are produced. Two hypothesis about what happens next are (1) Immune complexes composed of virus and antibody are formed that activate the complement causing increased vascular permeability and thrombocytopenia (low platelet count). (2) The antibody increases the entry of virus into the monocyte and macrophages with the consequent liberation of a large amount of cytokines. In either scenario shock or hemorrhage occurs.
(C) Protein disulfide isomerase (PDI) is one of the candidate self-antigens recognized by anti-DV NS1 antibodies. PDI is mainly localized in the endoplasmic reticulum. PDI mediates platelet aggregation and secretion by activating aI Ib b3 integrin. Dengue virus induces cell surface expression of PDI and subsequent up regulation and / or activation of b1 and b3 integrin’s, which facilitated DV infection into endothelial cells.
The WHO (world health organization) classification and grading of dengue fever are as below;
It is very common.
Symptoms usually begin with history of sore throat, high grade fever, severe malaise, headache, pain in the eyes, myalgia (pain in the lumbosacral region and legs), nausea, vomiting, abdominal pain and diarrhea.
In children, sore throat and abdominal pain are the predominant symptoms.
It is usually followed by minor hemorrhagic spots or red rasheson the trunk, limbs, face, etc.Some severe cases may present with acute gastrointestinal bleeding and shock. The illness lasts 5 to 7 days.
The prominent feature is low blood pressure (due to less fluid in the body). The other clinical features include fever, weak pulse with very low blood pressure, cold and clammy skin. Neurological problems are seen like restlessness, lethargy, altered state of consciousness, fits, coma, etc. Pleural effusion (abnormal accumulation of fluid in the lungs), ascites (abnormal accumulation of fluid in the abdomen) and intense abdominal pain may also be present.
The prominent feature is bleeding. Petechiae (small pin point red dots), purpura (large dots), bleeding from the nose, gum bleeding, blood in stool, etc. are common.
The early phase of DHF is indistinguishable from dengue fever. After 2 - 5 days, a few cases in the first infection, in contrast with a significant number of cases after reinfection by another serotype may present with low platelets (less than 100,000 / microliter or even less than 20,000 / microliter) and hemo-concentration (increase hemoglobin concentration).
Liver enlargement and tenderness may be present. The spleen is not palpable / enlarged.
Other manifestations include pleural effusion (abnormal accumulation of fluid in the lungs) and low serum/blood albumin, encephalopathy (coma, etc.) with normal cerebrospinal fluid.
Diffuse leakage of plasma from the capillaries / blood vessels is responsible for the hemo-concentration. In the presence of hemo-concentration and low platelets, the patient is considered as suffering from dengue hemorrhagic fever and is classified as below according to the World Health Organization classification.
DHF Grade I – low platelets + hemoconcentration with absence of spontaneous bleeding.
DHF Grade II - low platelets + hemoconcentration with presence of spontaneous bleeding.
DHF Grade III - low platelets + hemoconcentration with hemodynamic instability (low plasma volume with weak pulse, low blood pressure &cold extremities), and mental confusion.
DHF Grade IV - low platelets + hemoconcentration, with shock, patient will be pulse-less and with non-recordable blood pressure (dengue shock syndrome).
The fatality rate from dengue hemorrhagic fever / dengue shock syndrome is 25-50% or higher if untreated. With supportive treatment the fatality rate is less than 5%.
Some patients would experience depression and fatigue for several months after recovery.
Complete blood count (CBC) should be done on daily basisto monitor platelet count and deterioration / improvement.
- PCV / HCT % (Hematocrict) ranges from 19.2% to 55.5%, it is usually high (> 45%) in DHF / DSS due loss of plasma from the vessels).
- Low white blood cell count, low neutrophil count, increase lymphocytes.
- Moderately low platelets in Dengue fever which is usually below 100,000 / micro liters and severely low in Dengue hemorrhagic fever usually below 20,000 / micro liters
Blood Test for dengue antibodies / antigens (dengue virus)
Soon after any infection, the human body first form IgM antibodies and after two weeks starts forming IgG antibodies.
IgM antibodies test against dengue virus:These antibodies are detectable in more than 65 % of the patients usually after 6-8 days of illness. Serum collected early may give false negative resul (because the human body takes few days to produce considerable amount of IgM antibodies after which the machines / kits are able to detect them). Sometimes the IgM antibodies may remain detectable for 1-2 months.
IgM Positive result may suggest recent infection with Dengue fever.
However definitive diagnosis can only be made if the virus is isolated or the virus genome is detected by antigen based kits / devices / PCR. This is because the machine / kits may detect some other antibodies which are similar to dengue antibodies (this is called cross reaction) and the patient will be misdiagnosed as dengue fever, infact he may be suffering from some other disease.
Once the IgG antibodies are produce, they will remain in the body for years. IgG antibody test is not done.
(Presence of IgM antibodies against dengue virus indicates recent infection while IgG indicates past infection).
Coagulation test like PT / APTT should be done on daily basis to monitor deterioration / improvement.
Liver function test
Commonly the liver enzyme SGPT level is increased.
Radiology
Chest x-ray shows pleural effusion (abnormal accumulation of fluid in the lungs) and occasionally pericardial effusion (abnormal accumulation of fluid around the heart)
Ultrasound
Ultrasound is done to detect pericardial effusion and ascites (abnormal accumulation of fluid in the abdomen).
There is no specific treatment.
1. Dengue Fever
Oral fluid, analgesics and antipyretics (paracetamol) are the main therapy.
2. Dengue Hemorrhagic fever / Dengue Shock Syndrome
These patients require hospitalization as the mortality can be as high as 40% if not treated.
In the hospital, pulse, blood pressure, temperature, Level of consciousness, fluid input and output,blood Hematocrit and platelets count counts are monitored.
Intravenous fluid (Ringer’s lactate) followed by other fluids/drips are given to cover the loss of fluid.
Transfusion of Platelets is mandatory if the count is below 20,000/microliters.
Steroid therapy is not helpful.
Approximate hospital stay is 4 - 7 days.
- Observation for at least 3 days after recovery from shock
- No respiratory distress due to pleural effusion or ascites
- Platelet count more than 50,000
- Absence of fever for more than 24 hours
- Return of appetite
The average cost of management of a patient in a private hospital with Dengue Fevervaried from 20,000 to 40,000 Pak rupees. In case, the patients requiring critical care stay for Dengue Shock Syndrome / Dengue Hemorrhagic Fever the cost is as high as 100,000 to 200,000 PKR for 3-4 days.
Late diagnosis and delayed hospitalization increases the cost of disease management and has a high mortality rate.
With early supportive treatment, 95% of cases recover rapidly and without sequelae. Hospitalized patients can return to their houses after 2-4 days if they are without fever.
5% of the patients suffer Dengue Hemorrhagic Fever and 5-10% deaths have been reported even with supportive treatment.Most fatal cases are seen among the children and young adults.
High mortality in patients may be due to reinfection with other dengue virus subtype, late hospitaliztaion and lack of uniformity in patient management.
There is no vaccine to protect against dengue. Vaccine development is difficult since any of four different dengue serotypes may cause the disease.
Avoid drugs like Aspirin, NSAIDS, Brufen as it may aggravate bleeding.
There is no vaccine to protect against dengue.
Prevention at community level
Vector control by use of insecticidal fumigation, etc.
Mass education programs for the general population and medical practitioners about the disease, its early diagnosis and management.
Prevention at individual level
Use mosquito repellants.
Wear full sleeves shirts / cover all areas of the body.
Mosquito nets.
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