Clinical infectious disease - treatment of dengue fever
Clinical infectious disease - treatment of dengue fever
Dengue fever is caused by day biting of the Aedes aegypti mosquito which typically present in the tropical countries. Dengue fever is a viral disease with the mosquito acts as a vector. There are four serotypes of this single stranded RNA flavivirus. It is difficult to eradicate dengue fever based on the fact that the mosquito lives indoors with people and not in the external environment.
The centre for disease control and prevention has concluded that dengue fever is the most important and common mosquito borne viral disease infecting human. It happens in urban and rural areas. Annually it is estimated that 50 - 100 million people are admitted due to dengue fever. Beside that 250 000 and 500 000 individuals are suffering from dengue hemorrhagic fever (one of the variant of dengue fever). It is reported that 2400 deaths occur annually. Over the years, there has been a case of dengue fever in non endemic countries such as the United Kingdom and United States due to improvement of the transport system such as travel which increase the speed of transmission. Traveler in tropic countries carries a moderate risk of dengue fever infection and based on statistic, it affects 1 in 10 travelers.
Dengue fever is caused by flavivirus . The flavivirus is made up from single stranded of RNA. There are 4 different serotypes (variants) of the RNA of the flavivirus and each them coded for different form of infection in term of severity, signs, symptoms, pathological finding and treatment. Developing lifelong immunity towards one of the RNA serotypes does not protect you from infection from the other RNA stereotypes. There is a minimal case of cross immunity. A patient who suffers from secondary infection of dengue fever by different serotypes of the RNA will appear to be more seriously ill. This is based on the concept of antibody dependent enhancement mechanism. In this concept, the antibodies that develop from the first dengue fever will enhance the individual susceptibility towards infection from the second stereotypes.
After being bitten by the mosquito patient initially appear to be asymptomatic. After the incubation period of 2- 7 days have passed patient starts to develop the symptoms. The symptoms are categorized into undifferentiated febrile illness, (the least severe), dengue fever, dengue hemorrhagic fever and dengue shock syndrome (the most severe).For traveler who is infected with flavivirus, he may present with acute febrile illness soon after returning from the travel.
Undifferentiated febrile illness is the least severe presentation of the dengue fever. It is difficult to differentiate it from other form of symptoms of viral infection. The patient typically develops flu like symptoms and recovers fully.
Symptoms of dengue fever mostly develop as a result of primary and secondary infections. Dengue fever is presented with sudden onset of fever. The fever is typically presented for 2- 7 days and the patient may recover. However the patient may present with ‘Saddleback fever ‘where the fever tends to recur again follow by a recovery phase for several days and return again. (Biphasic pattern). Besides fever, the patient also suffers from malaise and retro orbital headache. Other signs include conjunctiva injection, puffiness of the eyelid and flushing of the face which is known as dengue facies. The patient also may develop erythematosus macular rash. This rash will begin on the trunk before spreading to the limbs. The patient also tends to be anorexic with abdominal discomfort. In severe case, patient may suffer from “break bone fever” that is presented with myalgias and athralgias. Some patients may develop dengue haemorrhagic fever and most will recover with a prolonged recovery period.
Dengue haemorrhagic fever is another form of dengue fever presentation. Dengue haemorrhagic fever is rare, life threatening condition. It mostly affects individuals < 16 years old. (flavivirus is endemic). Dengue haemorrhagic fever is associated with secondary infection due to antibody dependent enhancement system. (An antibody that develops from previous stereotypes enhanced infection of other stereotypes). Primary infection from dengue haemorrhagic fever is rare.
Dengue haemorrhagic fever carries a similar presentation as dengue fever. The patient may present with sudden onset / intermittent high fever, malaise, retro orbital headache, flushing, anorexia, abdominal pain and vomiting. Additional features of haemorrhage may present that includes haematemesis, Malena, epistaxis, gum bleeding, ecchymoses and petechiae as well as heavy vaginal bleeding in female. The most concerning features of dengue haemorrhagic fever are circulatory failure which is associated with plasma leakage. Plasma leakage is presented with hypotension, tachycardia, delay capillary refill and normal pulse volume as well as pleural effusion and ascites. Dengue haemorrhagic fever may present with rare complication such as myocarditis, encephalitis, liver failure, brain encephalopathy and disseminated intravascular coagulation.
Dengue haemorrhagic fever is classified based on the WHO grading scale
Grade 1: Patient is negative for shock but present with positive tourniquet test.
Grade 2: Patient is negative for shock but present with positive tourniquet test and suffers from spontaneous bleeding.
Grade 3: Patient suffers from shock
Grade 4: Patient suffers from profound shock with immeasurable pulses and blood pressure.
Dengue shock syndrome is the most lethal and severe form of dengue fever. It carries a high mortality rate (9 % - 45 %). The most common cause of death from dengue fever is due to dengue haemorrhagic shock follows by dengue haemorrhagic fever. Patient presented with profound shock. The pulse pressure < 20 mm Hg and the systolic blood pressure is < 80 mm Hg. Aggressive supportive treatment is required.
Summary of the different types of dengue infection
*Undifferentiated febrile illness
Two or more of the following should be present to confirm this acute illness that include rash, myalgia, athralgia, headache, hemorrhagic manifestation as well as retro - orbital headache and leukopenia.
*Dengue hemorrhagic fever
-All of the criteria should be present to confirm the diagnosis of dengue hemorrhagic fever such as the present of bleeding gum , positive tourniquet test, ecchymoses, petechiae or evidence of gastrointestinal bleeding.
*Dengue shock syndrome
All the criteria should present to confirm the diagnosis such as hypotension with systolic blood pressure < 20mmHg and pulse pressure < 20 mm Hg with haemorrhagic manifestation.
Laboratory investigation for dengue fever may include full blood count, urea, electrolytes and creatinine level, blood urea nitrogen and liver function test and coagulation studies. Laboratory investigation is normal in almost all dengue fever patients. However in severe cases the blood test of the patient may reveal thrombocytopenia < 100 000 / mm3 and leukopenia. The patient may also present with abnormal liver function test. All these results provide an indication of the development of disseminated intravascular coagulation ( DIC ). The technique that is used to confirm the presence of flavivirus includes serology testing, virus isolation and amplification of the DNA. However these procedures are rarely performed and the diagnosis is made clinically.
Dengue fever should be treated to avoid any complication of the later stages. The treatment is not specific. There are no drugs, medication or pharmacological agents that are presented specifically for dengue fever. Mostly the treatment for dengue fever is supportive. Acetaminophen is prescribed to the patient who is feverish. Aspirin or any aspirin containing agent should be avoided in any children with viral infection as it may lead to Reiter Syndrome.
In more severe cases of dengue haemorrhagic fever as well as a dengue shock syndrome, early identification and management of plasma leakage is essential. Plasma leakage may be presented with tachycardia, narrow pulse pressure and haemato- concentration. This is more obvious with hypotension as well as overt bleeding.
The management of plasma leakage may include intravenous infusion of crystalloid solution. This is followed by monitoring of the vital signs, urinary output and mental states. Litres of fluid may be required and should be given to the patient.
Complications that develop from gastrointestinal bleeding should be treated with transfusion of the blood, fresh frozen plasma and platelet. Patient with disseminated intravascular coagulation (DIC) should be managed in it's usual way.
Low threshold should be used in deciding if the patient required admission as dengue fever is managed mostly in the outpatient department. Patient who suffers from dengue hemorrhagic fever or dengue shock syndrome or for children who is suspected with dengue hemorrhagic fever should be monitor and admitted for development of shock or significant bleeding complication.
Recovery from dengue fever is prolonged with fatigue often lasting for months after the illness.
Research has been done to develop a vaccine against dengue fever. However until today, this effort has not been clinically proven to be beneficial. The major obstacle in developing a vaccine is to create a tetravalent vaccine which will act against the 4 serotypes of the flavivirus and able to avoid the concept of antibody dependent enhancement.
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