Singapore hemorrhagic fever



OVERVIEW

Definition

Dengue fever is an acute infectious disease caused by dengue virus infection, mainly transmitted by Aedes aegypti mosquitoes.

Types

According to the severity of the disease, dengue fever can be categorized into two clinical types: typical dengue fever and severe dengue fever.

Incidence

Endemic areas

Dengue fever is mainly endemic in tropical and subtropical regions, and is most common in Southeast Asia and the islands of the Western Pacific.

In some countries in Southeast Asia, dengue fever has become endemic and can occur throughout the year.

According to the World Health Organization, prior to 1970, only nine countries had experienced epidemics of severe dengue fever.

The disease is now endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, Southeast Asia and the Western Pacific.

The first dengue epidemic in China occurred in 1978 in Foshan City, Guangdong Province.

With the warming of the climate and the convenience of transportation, the provinces in China where dengue fever cases have appeared have gradually expanded to the north.

Epidemic Situation

Millions of people are infected with dengue fever globally each year, and there have been many regional epidemics around the world.

As the disease spreads to new places, not only is there an uptick in the number of cases, but outbreaks are also occurring.

An estimated 500,000 cases of severe dengue fever require hospitalization each year, and an estimated 2.5% of cases die each year.

Causes

Causes

The causative agent of dengue fever is the dengue virus, and there are 3 basic conditions that lead to epidemics.

Source of infection: patients and latently infected persons, most contagious within 1 to 3 days of the onset of the disease, and in a few patients, the virus can be isolated from the blood on the 3rd day after the fever has subsided.

Transmission: Bites of Aedes mosquitoes (including Aedes aegypti and Aedes albopictus).

Susceptible population: The population is generally susceptible and can be infected twice.

Pathogenesis

The pathogenesis of dengue fever is not clear.

It is generally believed to be associated with viral factors, antibody-dependent infection enhancement phenomenon, cytokine storm, host genetic factors and autoimmunity.

Severe dengue fever is mainly due to increased vascular permeability and plasma extravasation, which allows a large amount of plasma to enter the lumen during the withdrawal phase of the fever, decreasing blood volume and concentrating the blood, triggering shock.

Symptoms

The incubation period of dengue fever (the time of infection without onset of disease) is usually 3 to 15 days, mostly 5 to 8 days, and the length of incubation time is related to the amount of invading virus.

After the onset of the disease, the symptoms of different types of dengue fever vary.

Typical dengue fever

The typical course of dengue fever is divided into three phases, i.e. the acute febrile phase, the extreme phase (the most severe period of disease progression) and the recovery phase.

Acute fever stage

Sudden onset of high fever, body temperature rapidly reaches 39 ℃ or above, lasting 2 to 7 days and then suddenly drop to normal, may be accompanied by chills.

There may be bimodal fever, also known as saddle fever, that is, some patients in the course of the third to fifth day of the body temperature dropped to normal, and then rose again after one day.

There may be generalized muscle, bone and joint pain.

In children, the onset of the disease is slow, the fever is low, and the fever may be accompanied by headache, back pain, muscle and joint pain, orbital and retro-orbital pain, and other systemic symptoms.

It appears within 2 to 5 days of onset.

The rash initially occurs on the palms, soles of the feet, or trunk and abdomen, progressing to the neck and extremities, and may also appear on the face.

The rash appears as maculopapular rash, measles-like rash, scarlet fever-like rash, erythematous rash with discoloration on pressure, and in severe cases, hemorrhagic rash.

It is slightly itchy, and some people may have strange itching.

Rash can last for 3-4 days, most of them subside at the same time with fever, and there are also cases in which the rash is more obvious after the body temperature drops.

There is no flaking or hyperpigmentation after the rash subsides.

In 5～8 days after the onset of the disease, 25%～50% of the cases may appear multi-site, varying degrees of hemorrhage.

The manifestations are nosebleeds, skin petechiae, gastrointestinal bleeding, hemoptysis, hematuria.

Women may have vaginal bleeding.

Generalized lymph nodes may be mildly enlarged with mild tenderness.

There may be gastrointestinal symptoms such as nausea, vomiting, abdominal pain, poor appetite, diarrhea and constipation.

The face and conjunctiva of the eyes are congested, and the skin of the neck and upper chest is flushed.

A relatively slow pulse may be present, and in severe cases there may be fatigue and weakness in a state of exhaustion.

Occasionally, jaundice (yellowing of the sclera and mucous membranes of the skin) may occur.

During the febrile period, the patient has worsening abdominal pain or significant abdominal pressure and persistent vomiting.

Pleural effusion and ascites appear.

Bleeding of mucous membranes.

Presence of lethargy or irritability.

Extreme stage (the most serious period of disease progression)

Appears within 3～7 days of disease course, body temperature drops to 37.5～38℃ or below, pleural effusion, ascites, etc. may appear as follows.

Appears within 4 to 5 days of disease course and usually lasts 12 to 24 hours.

Restlessness, lethargy, cold extremities, pallor, and patterned skin.

The body temperature falls, and the respiration is rapid and irregular.

The pulse is weak, the pulse pressure decreases progressively, and the blood pressure falls or is even undetectable.

There may be occasional coma during the course of the disease, and if not rescued in time, death may occur within 4 to 10 hours.

Bleeding tendency is severe with nosebleeds.

Massive petechiae appear on the skin, vomiting blood, blood in the stool, hemoptysis, hematuria, vaginal bleeding, and even intracranial hemorrhage.

Severe hepatitis, encephalitis, myocarditis, or severe hemorrhagic symptoms such as jaundice, coma, palpitations, chest pain, and weak pulse may occur.

If the disease progresses rapidly, death can occur due to central respiratory failure and hemorrhagic shock.

Recovery period

It occurs 5 to 7 days into the disease and 48 to 72 hours after the extreme phase.

Fever subsides.

Appetite is restored.

The disease is often followed by a feeling of weakness and depression.

Some patients may have itchy skin and bradycardia, and full recovery often takes several weeks.

Severe Dengue Fever

Severe hemorrhage

Subcutaneous hematoma, vomiting blood, black stools, vaginal bleeding, hematuria of the naked eye, intracranial hemorrhage, etc.

Shock

Tachycardia, cold and clammy extremities, prolonged capillary filling time (the time it takes for blood to refill the nails or localized skin to turn white by pressing on it and then rapidly relaxing it) > 3 seconds, weak or undetectable pulse, or undetectable blood pressure, etc.

Severe organ damage

Liver injury, acute myocarditis, acute renal failure, encephalopathy and encephalitis with manifestations such as chest pain, palpitations, oliguria or anuria, and coma.

Complications

Acute myocarditis and acute heart failure

Panic, chest tightness, shortness of breath, clammy and cold extremities, cyanosis (bluish skin and mucous membranes).

Encephalitis

Severe headache, projectile vomiting, impaired consciousness, and limited limb movement.

Acute renal failure

Oliguria or anuria, severe edema.

Toxic hepatitis

Jaundice, can have coma and other manifestations of hepatic encephalopathy.

Consultation

Department of Medicine

Dermatology

If you have a rash that fades on pressure or a hemorrhagic rash, you may consult a dermatologist and be referred to an infectious disease department after confirmation of the diagnosis.

Department of Infectious Diseases

If you have visited a dengue-endemic area before the onset of the disease, or if there are confirmed cases in the surrounding area and symptoms such as fever, rash, bleeding, and muscle pain are present, it is recommended that you consult the doctor promptly.

Emergency Department

It is recommended to go to the Emergency Department immediately in case of emergencies such as high fever, convulsions, severe bleeding, difficulty in breathing, confusion, irritability, and cold and wet limbs.

Preparation for medical treatment

Preparation for medical consultation: registration, preparation of information, common problems

Tips for seeking medical treatment

A full body physical examination is often required, and imaging tests may be performed. It is recommended to wear loose-fitting clothing, avoiding clothing made of metal, and to inform the doctor in advance if you are pregnant or planning to become pregnant.

For patients with high fever, physical cooling can be done first, such as applying cold compresses to the forehead and wiping the hands, feet and armpits with lukewarm water.

Preparation checklist for medical consultation

Pay special attention to the time of onset of symptoms, special manifestations, etc.

Is there fever? What is the highest degree?

Is there a rash? How long has it been there? What is the order of appearance of the rash?

Is there joint pain, muscle pain?

Is there any bleeding from the nose, gums, or vagina?

Have you been bitten by mosquitoes recently?

Have you traveled to a dengue-affected area in the last two weeks?

Are there any autoimmune deficiency diseases, or immunocompromised?

Test results in the last 6 months, which can be brought to the doctor’s office

Laboratory tests: blood tests

Imaging tests: abdominal ultrasound, cardiac ultrasound, chest CT, head CT and MRI

Medications in the last 3 months, bring the box or package with you if available

Antipyretic and analgesic medications: ibuprofen, acetaminophen

Hemostatic medications: carbachol, vitamin K

Glucocorticoids: prednisone

Diagnosis

Diagnosis is based on

Medical history

Residence in or visit to an endemic area within 2 weeks of dengue fever.

Presence of dengue cases within 1 month around residence or workplace.

Clinical manifestations

During the epidemic season there is sudden onset of illness, fever with muscle, bone and joint pain.

Flushing of the face and slow pulse.

Superficial lymph nodes are enlarged.

Rash, leukopenia and thrombocytopenia appear 2 days after the onset of fever.

Laboratory tests

The total number of leukocytes is decreased at the onset of the disease and is more pronounced during the rash.

The percentage of neutrophils appears to be decreased, with a relative increase in lymphocytes, and toxic granules and a marked leftward shift of the nucleus are seen.

There are abnormal lymphocytes, and the blood picture returns to normal 1 week after the fever is gone.

Thrombocytopenia may be present in 1/4 to 3/4 of the population, down to 13 x 109/L.

There may be a small amount of protein, red blood cells, white blood cells, and sometimes tubular pattern.

Blood concentration, prolonged bleeding and clotting times are seen.

Prolonged prothrombin time.

Various coagulation factors are mildly decreased, fibrinogen is decreased, and fibrinogen degradates are mildly to moderately increased.

Virus isolation is the gold standard for confirming the diagnosis of dengue fever, in the early stages of the disease, with high sensitivity. However, it is rarely performed clinically.

The diagnosis is aided by the absence of previous disease with this group of viruses, a high antibody potency on serologic tests, or a fourfold or greater increase in antibody potency during the recovery period.

Positive IgM antibodies help in the early clinical diagnosis of dengue.

If IgG is detected early in the disease, it indicates acute infection, and a titer of ≥1:80 is informative for diagnosis.

Detection of dengue virus antigen in serum can be used as a basis for definitive diagnosis.

Diagnosis can be made 5-6 hours after viral infection.

The virus can be typed within 2 days of viral infection.

High sensitivity, high specificity and short detection time.

It can be used for rapid and early diagnosis of dengue fever.

Imaging examination

There may be heart enlargement, pleural effusion.

Thoracic and abdominal CT may show pleural effusion, pericardial effusion ascites, and in a few cases, subcutaneous hematoma or exudation is found.

Head CT and MRI may reveal cerebral edema, intracranial hemorrhage, etc.

Abdominal ultrasound may reveal thickening of the gallbladder wall, ascites and hepatosplenomegaly.

Cardiac ultrasound may show diminished myocardial pulsation, and in severe cases, cardiac enlargement and decreased left heart ejection fraction.

Electrocardiography

Conduction block and non-specific ST-segment elevation, T-wave inversion, and various arrhythmias can be found.

Differential Diagnosis

Differential Diseases

Fever with rash should be differentiated from influenza, yellow fever, leptospirosis, typhus, typhoid fever, malaria, measles, scarlet fever, and drug rash.

Severe dengue fever should be distinguished from epidemic hemorrhagic fever, meningococcal septicemia and rickettsial disease.

Fever with severe bone and joint pain should be differentiated from Chikungunya fever.

If the fever with bleeding symptoms is obvious, it needs to be differentiated from renal syndrome hemorrhagic fever, fever with thrombocytopenia syndrome, and so on.

Encephalopathic manifestations should be differentiated from other central nervous system infections.

Those with significant leukocyte and thrombocytopenia should be differentiated from hematologic disorders.

Identification methods

Epidemiology, serologic tests, and nucleic acid tests are useful in making a better differential diagnosis.

Treatment

Aims and principles of treatment

There is no specific treatment or specific drug for dengue fever.

Treatment is mainly to improve the symptoms and prevent deterioration of the patient’s condition and spread of the epidemic.

The use of drugs needs to strictly follow the doctor’s instructions and avoid self-adjustment of dosage or discontinuation of drugs.

Treatment

General treatment

According to the epidemic scale, if there is an outbreak of the epidemic, those with mild symptoms and no risk factors for serious illness can be treated with home isolation according to the needs of epidemic prevention and control, and live in isolation rooms with anti-mosquito equipment.

If the symptoms are more severe or there are high risk factors for serious illness, hospitalization for isolation, observation and treatment is recommended.

In the acute stage, bed rest should be provided until the body temperature and platelet count return to normal and there is no bleeding tendency before appropriate activities are allowed.

Attention should be paid to clean the mouth and skin, and keep the feces clear.

Fluid and semi-fluid foods that are high in protein, vitamins and sugar and are easy to digest should be consumed, for example, moderate amounts of protein powder, noodle soup, fruit juice and vegetable juice can be combined with food.

Drink plenty of fluids to maintain water and electrolyte balance.

Symptomatic treatment

For patients with high fever, physical cooling should be used first, such as ice packs, alcohol swabs, and then acetaminophen can be given, which can have analgesic and antipyretic.

For analgesic and antipyretic drugs should be used carefully according to medical advice, such as aspirin (acetylsalicylic acid), naproxen, ibuprofen and so on.

For those with high fever that does not go away and severe toxemia symptoms, small doses of adrenocorticotropic hormone can be applied for a short period of time, such as oral prednisone.

For those with excessive sweating and diarrhea, oral rehydration should be used first, paying attention to water, electrolyte and acid-base balance.

Intravenous rehydration should be used when necessary to correct dehydration, hypokalemia and metabolic acidosis.

Always be alert to the possibility of inducing cerebral edema, intracranial hypertension, and brain herniation.

Early intravenous rehydration therapy is effective in reducing the likelihood of shock and decreasing the severity of the disease.

In cases of severe headache and intracranial hypertension, rapid intravenous drip of 20% mannitol injection should be applied promptly.

Intravenous dexamethasone helps to reduce cerebral edema and lower intracranial pressure.

Patients with respiratory center inhibition should be promptly treated with artificial respirator.

For those with bleeding tendency, general hemostatic drugs such as carbachol and vitamin K are given, and whole blood or platelets can be transfused when the bleeding is large.

For patients with severe pain can be appropriate use of sedative drugs, according to the specific circumstances, follow the doctor’s instructions to take.

Patients with severe dengue fever should pay attention to fluid resuscitation treatment, and the initial fluid resuscitation treatment is based on isotonic crystalloid.

If the above treatment is ineffective or the degree of shock is more serious, colloidal solution is added, and the acid-base imbalance is promptly corrected according to the actual situation.

Vasoactive drugs may be used when blood pressure cannot be maintained by fluid resuscitation.

Shock caused by severe bleeding should be promptly transfused with red blood cells and whole blood, etc.

Prognosis

Cure

Dengue fever is a self-limiting disease and most have a favorable prognosis, with the duration of illness ranging from 7 to 10 days.

There is a difference in prognosis between severe and non-severe patients.

Hazards

Multiple organ failure may occur in severe dengue fever, leading to death.

Daily

Daily Management

Dietary management

It is advisable to consume high-protein and low-fat foods, such as milk, soy products, eggs and lean meat.

Eat plenty of food such as fresh vegetables and fruits to supplement vitamins.

Work and rest management

Take rest during fever, avoid exertion, and ensure sufficient sleep and rest to promote recovery.

Psychological regulation

Maintaining good emotional stability can help improve immunity and promote recovery.

Prevention

Maintain environmental hygiene to minimize the breeding of mosquitoes

Household water storage containers should be covered and emptied and cleaned weekly.

Use insecticides on outdoor water storage containers, including those that kill eggs.

Do not have standing water in planters and other containers in your home.

On rainy days on the ground, in pots, tanks, cans, caverns and other places prone to stagnant water should be cleaned up in a timely manner, and sprayed with mosquito killer to reduce mosquito density if necessary.

Individual daily protection

In areas where dengue fever is endemic, families use screen doors, screen windows, mosquito nets, mosquito coils, etc., and sleep in air-conditioned rooms in summer.

Wear long sleeves and long pants and do not camp in the wild.

Individuals should pay attention to the use of anti-mosquito repellent liquid, anti-mosquito stickers, etc. to prevent Aedes mosquito bites.

When you go out during the day, use mosquito repellent with effective concentration of mosquito repellent.

Pay attention to a balanced diet, nutrition, work and rest, appropriate exercise, enhance physical fitness.

Mosquito bites appear after fever, headache, muscle pain and other discomforts, early detection, early diagnosis, timely isolation and treatment.