Dengue Signs & Clinical Symptoms

After being bitten by a mosquito carrying the dengue virus, the incubation period ranges from 3 to 14 (usually 4 to 7) days before the signs and symptoms of dengue appear. Dengue occurs in two forms: Dengue Fever (DF) Dengue Haemorrhagic Fever (DHF)

Figure 1: Dengue fever symptoms. A: Hospital with dengue patients, B: Dengue fever rash, C: Patient with dengue hemorrhagic fever

Dengue Fever The disease manifests as a sudden onset of severe headache, chills, pain upon moving the eyes, and low backache. Painful aching in the legs and joints (myalgias and arthralgiassevere pain that gives it the nickname break-bone fever or bonecrusher disease) occurs during the first hours of illness. The temperature rises quickly as high as 40 C, with relative low heart rate (bradycardia) and low blood pressure (hypotension). The dengue rash is characteristically bright red petechiae and usually appears first on the lower limbs and the chest (see figure 2). The glands (lymph nodes) in the neck and groin are often swollen. In some patients, it spreads to cover most of the body. There may also be gastritis with some combination of associated abdominal pain, nausea, vomiting, or diarrhea. Some cases develop much milder symptoms which can be misdiagnosed as influenza, chikungunya, or other viral infection when no rash is present. The classic dengue

fever lasts about six to seven days, with a smaller peak of fever at the trailing end of the disease (the so-called biphasic pattern). Clinically, the platelet count will drop until the patient's temperature is normal.

Recognition of Dengue fever Sudden onset of high fever Severe headache (mostly in the forehead) Pain behind the eyes which worsens with eye movement Body aches and joint pains Nausea or vomiting

Figure 2: Typical dengue fever symptoms, patients with dengue fever rash

Dengue Haemorrhagic Fever Dengue hemorrhagic fever (DHF) is caused by the same viruses and is characterized by increased vascular permeability, hypovolemia and abnormal blood clotting mechanisms. DHF is a potentially deadly complication with symptoms similar to those of dengue fever, but after several days the patient becomes irritable, restless, and sweaty. The illness often begins with a sudden rise in temperature accompanied by facial flush and other flu-like symptoms. The fever usually continues for two to seven days and can be as high as 41C, possibly with convulsions and other complications. In moderate DHF cases, all signs and symptoms abate after the fever subsides. In severe cases, the patient's condition may suddenly deteriorate after a few days of fever; the temperature drops, followed by signs of circulatory failure, and the patient may rapidly go into a critical state of shock. The Dengue Shock Syndrome (DSS) is characterized by bleeding that may appear as tiny spots of blood on the skin (petechiae) and larger patches of blood under the skin

(ecchymoses). Minor injuries may cause bleeding (see figure 4). Shock may cause death within 12 to 24 hours. Patients can recover following appropriate medical treatment.

The progress towards DHF or DSS occur after 3-5 days of fever (see figure 3). At this time, fever has often come down. This may mislead many of us to believe that the patient is heading towards recovery. In fact, this is the most dangerous period that requires high vigilance from care-givers.

Figure 3. Generalized time course of the events associated with DF, DHF and DSS. The incubation period before the development of signs of infection generally ranges from 4 to 7 days. Recognition of Dengue Haemorrhagic Fever (DHF) Symptoms similar to dengue fever plus, any one of the following: Severe and continuous pain in abdomen Bleeding from the nose, mouth and gums or skin bruising Frequent vomiting with or without blood Black stools, like coal tar Excessive thirst (dry mouth) Pale, cold skin Restlessness, or sleepiness

Dengue shock syndrome is defined as dengue hemorrhagic fever plus: Weak rapid pulse Narrow pulse pressure (less than 20 mm Hg)

 Cold, clammy skin and restlessness.

Figure 4: Patients with dengue hemorrhagic fever

Diagnosis of Dengue

The diagnosis of dengue is usually made clinically. The classic picture is high fever with no localising source of infection, a petechial rash with thrombocytopenia and relative leukopenia (low platelet and white blood cell count). Care has to be taken as diagnosis of Dengue Haemorrhagic Fever (DHF) can mask end stage liver disease and vice versa. If one has persistent fever for more than 2 days then one should go for a complete blood checkup (CBC). If the platelet count and WBC count are below than their usual range one should go for Dengue Antigen test. Dengue is always a diagnosis of exclusion, and other diseases with the same initial clinical presentation must be suspected. In order to help the clinician in the detection of severe forms of dengue (DHF/DSS), even when the definitive diagnosis has not been made yet, the following three essential laboratory tests may help in the evaluation of the real clinical conditions of the patient and its early supportive management:

Total White Blood Cells Count: In case of dengue, this test will reveal leukopenia. The presence of leukocytosis and neutrophilia excludes the possibility of dengue and bacterial infections (leptospirosis, meningoencephalitis, septicemy, pielonephritis etc.) must be considered. Thrombocytopenia (less than 100.000 per mm3): Total platelets count must be obtained in every patient with symptoms suggestive of dengue for three or more days of presentation. Leptospirosis, measles, rubella, meningococcemia and septicemy may also course with thrombocytopenia Hematocrit (micro-hematocrit): According to the definition of DHF, its necessary the presence of hemoconcentration (hematocrit elevated by more than 20%); when its not possible to know the previous value of hematocrit, we must regard as significantly elevated the results more than 45%.

Figure 1. Case definitions of Dengue Haemorrhagic Fever (DHF). For a diagnosis of DHF Grade I, each of the four criteria must be met. Fever that is not specific and with constitutional symptoms and the only haemorrhagic proof being a positive tourniquet test are being classified under Grade I. Grade II is similar to Grade I, but Grade II has specific haemorrhagic manifestations. Signs of circulatory failure or hypertension are graded under Grade III, and lastly, profound shock with pulse and blood pressure that is undetectable is under Grade IV. A dependable immediate information of the Dengue diagnostics in the rural areas can be performed by the introduction of Rapid Diagnostic Test kits which also differentiates between primary and secondary dengue infections. Serology and polymerase chain reaction (PCR) studies are available to confirm the diagnosis of dengue if clinically indicated. Dengue can be a life threatening fever.

Etiologic confirmation can be obtained by isolating infectious virus, demonstrating viral antigen by immunoassay, or viral genome by PCR in serum or blood. Serologic diagnosis is achieved by IgM antibody-capture by enzyme-linked immunosorbent assay (MAC - ELISA) in two blood specimen taken in a period of 14 days from each other. The first specimen, taken till the seventh day of the disease, can also be useful for virus isolation by inoculation of A. albopictus cells or adults mosquitoes, with specific indentification of virus by immunofluorescence tests employing monoclonal antibody reagents.

Postmortem diagnosis is made by virus isolation or by demonstration of viral antigen (direct immunofluorescence) from two-specimen visceral fragments (liver, spleen, linfonodes, thymus).

Treatment of Dengue

Because dengue is caused by a virus, there is no specific medicine or antibiotic to treat it, the only treatment is to treat the symptoms. For typical dengue, the treatment is purely concerned with relief of the symptoms (symptomatic). Rest and fluid intake for adequate hydration is important.

Treatment The mainstay of treatment is timely supportive therapy to tackle shock due to hemoconcentration and bleeding. Close monitoring of vital signs in critical period (between day 2 to day 7 of fever) is critical. Increased oral fluid intake is recommended to prevent dehydration. Supplementation with intravenous fluids may be necessary to prevent dehydration and significant concentration of the blood if the patient is unable to maintain oral intake. A platelet transfusion is indicated in rare cases if the platelet level drops significantly (below 20,000) or if there is significant bleeding. The presence of melena may indicate internal gastrointestinal bleeding requiring platelet and/or red blood cell transfusion.

People who suffer from dengue fever have no risk of death but some of them develop Dengue Haemorrhagic Fever (DHF) or Dengue Shock Syndrome (DSS). In some of these cases death can occur. If a clinical diagnosis is made early, a health care provider can effectively treat DHF using fluid replacement therapy. Adequately management of DHF generally requires hospitalization.

Aspirin Aspirin, Brufen and non-steroidal anti-inflammatory drugs should be avoided as these drugs may worsen the bleeding tendency associated with some of these infections. Patients may receive paracetamol preparations to deal with these symptoms if dengue is suspected. Doctors should be very careful when prescribing medicines. Any medicines that decrease platelets should be avoided.

Traditional treatment

In Brazilian traditional medicine, dengue is treated with cat's claw herb, which is for inflammation and does not prevent dengue. In Malaysia, dengue is treated by some using natural medicine. The treatment is speculated to be able to arrest and reverse the viral infection and prevent the disease from advancing into a critical stage, though no evidence has yet shown effectiveness. In Philippines dengue patients use tawa-tawa herbs and sweet potato tops juice to increase the platelets counts and revived the patients. These are traditional treatments nd are often not based on scientific medicine research.

Dengue Virus Transmission

Dengue viruses are transmitted to humans through the bites of infective female Aedes mosquitoes. The mosquitoes generally acquire the virus while feeding on the blood of an infected person. After virus incubation for eight to ten days, an infected mosquito is capable, during probing and blood feeding, of transmitting the virus for the rest of its life. There is no way to tell if a mosquito is carrying the dengue virus. Infected female mosquitoes may also transmit the virus to their offspring by transovarial (via the eggs) transmission, but the role of this in sustaining transmission of the virus to humans has not yet been defined. Infected humans are the main carriers and multipliers of the virus, and serving as a source of the virus for uninfected mosquitoes. The virus circulates in the blood of infected humans for two to seven days, at approximately the same time that they have a fever (see also clinical symptoms). Aedes mosquitoes may acquire the virus when they feed on an individual during this period. In parts of South East Asia and Africa, the transmission cycle may also involve jungle primates that act as a reservoir for the virus (see figure 1).

Figure 1. Transmission of dengue viruses. Dengue is most widely transmitted by the mosquito named Aedes aegypti (see video 1 and 2). The Aedes albopictus mosquito and other Aedes species also transmit disease in specific areas. Aedes polynesiensis, Aedes scutellaris and Aedes pseudoscutallaris in the Pacific Islands and New Guinea. Aedes polynesiensis in the Society Islands and Aedes niveus in the Philippines.

The Aedes mosquito prefers to breed in water-filled receptacles, usually close to human habitation. They often rest in dark rooms (e.g. in bathrooms and under beds) and breed in small

pools that collect in discarded human waste (see figure 2). Although they are most active during daylight hours, biting from dawn to dusk, mosquitoes will feed throughout the day indoors and during overcast weather.

Dengue virus transmission follows two general patterns: epidemic dengue and hyperendemic dengue.

Epidemic dengue transmission occurs when dengue virus is introduced into a region as an isolated event that involves a single viral strain. If the number of vectors and susceptible pediatric and adult hosts is sufficient, explosive transmission can occur, with an infection incidence of 25-50%. Mosquito-control efforts, changes in weather, and herd immunity contribute to the control of these epidemics. This is the current pattern of transmission in parts of Africa and South America, areas of Asia where the virus has re-emerged, and small island nations. Travelers to these areas are at increased risk of acquiring dengue during these periods of epidemic transmission.

Hyperendemic dengue transmission is characterized by the continuous circulation of multiple viral serotypes in an area where a large pool of susceptible hosts and a competent vector (with or without seasonal variation) are constantly present. This is the predominant pattern of global transmission. In these populations, antibody prevalence increases with age and most adults are immune. Hyperendemic transmission appears to be a major risk for Dengue Haemorrhagic Fever (DHF). Travelers to these areas are more likely to be infected than are travelers to areas that experience only epidemic transmission.