Dengue fever (DF)

Dengue viruses are arboviruses capable of infecting humans, and causing disease. These infections may be asymptomatic or may lead to;

1. “classical” dengue fever, or
2. dengue haemorrhagic fever without shock, or
3. dengue haemorrhagic fever with shock.

Magnitude of problem

Dengue fever and its severe forms dengue haemorrhagic fever (DHF) and dengue shock syndrome have become major international public health concerns. Dengue and DHF is endemic in more than 100 countries in the WHO regions of Africa, the Americas, Eastern Mediterranean, South-East Asia and Western Pacific. The South-East Asia and Western Pacific regions are most seriously affected. Detection of all four serotypes has now rendered the countries hyperendemic. The countries of South-East Asia region are divided into 3 categories.

Category A (Bangladesh, India, Indonesia, Maldives, Myanmar, Sri Lanka, Thailand and Timor-Leste)

• Major public health problem;
• Leading cause of hospitalization and death among children;
• Hyperendemicity with all 4 serotypes circulating in urban areas;
• Spreading to rural areas.

Category B (Bhutan, Nepal)

• Endemicity uncertain;
• Bhutan reported first outbreak in 2004;
• Nepal reported first indigenous case in 2004.

Category C (Korea)

• No evidence of endemicity.

Epidemiological determinants

Agent factors

(a) Agent: The dengue virus forms a distinct complex within the genus flavivirus based on antigenic and biological characteristics. There are four virus serotypes which areDENV-1, DENV-2, DENV-3 and DENV-4.

(b) Vector: Aedes aegypti and Aedes Albopictus

Transmission of disease

The Aedes mosquito becomes infective by feeding on a patient from the day before onset to the 5th day (viraemia stage) of illness. After an extrinsic incubation period of 8-10 days, the mosquito becomes infective, and is able to transmit the infection. Once the mosquito becomes infective, it remains so for life. The genital tract of the mosquito gets infected and transovarian transmission of dengue virus occurs when virus enters fully developed eggs at the time of oviposition.

Environmental factors

The population of Aedes aegypti fluctuates with rainfall and water storage. Its life span is influenced by temperature and humidity, survives best between 16°C-30°C and a relative humidity of 60-80%. It breeds in the containers in and around the houses.

Incubation period

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.

Clinical manifestations

Dengue virus infection may be asymptomatic or may cause undifferentiated febrile illness (viral syndrome), dengue fever(DF), or dengue haemorrhagic fever (DHF}including dengue shock syndrome (DSS}.

1. Undifferentiated fever

• Simple fever indistinguishable from other viral infection.
• Maculopapular rashes may accompany the fever.
• Upper respiratory and gastrointestinal symptoms are common

2. Classical dengue fever

• All ages are susceptible to dengue fever. Children usually have a milder disease than adults.
•  The illness is characterized by an incubation period of 3 to 10 days (commonly 5-6 days).
• Sudden onset, with chills and high fever, intense headache, muscle and joint pains.
• Within 24 hours’ retro orbital pain, on eye movements or eye pressure and photophobia develops.
• Other common symptoms- extreme weakness, anorexia, constipation, altered taste sensation, colicky pain, abdominal tenderness, dragging pain in inguinal region, sore throat, general depression.
• Fever is usually between 39°C and 40°C

3. Dengue haemorrhagic fever (DHF)

DHF is a severe form of dengue fever. The course of dengue illness can be divided into three phases.

1. Febrile phase: illness commonly begins abruptly with high fever accompanied by facial flushing and headache. Anorexia, vomiting, epigastric discomfort, tenderness at the right costal margin and generalized abdominal pain are common.
2. Critical phase: Progressive leukopenia followed by a rapid decrease in platelet count usually precedes plasma leakage. At this point patients without an increase in capillary permeability will improve, while those with increased capillary permeability may become worse as a result of lost plasma volume.
3. Recovery phase: If the patient survives a gradual reabsorption of extravascular compartment fluid. General well-being improves, appetite returns, gastrointestinal symptoms decrease, ,haemodynamic status stabilizes and diuresis occurs as a result. WBC count usually starts to rise soon after defervescence but the recovery of platelet count is typically later than that of WBC count.

4. Severe dengue

Severe dengue is defined by one or more of the following:

(i) plasma leakage that may lead to shock (dengue shock) and/or fluid accumulation, with or without respiratory distress, and/or (ii) severe bleeding, and/or (iii) severe organ impairment.

Criteria for clinical diagnosis

A summary of clinical diagnosis of DF and DHF is as follows:

Dengue fever

Probable diagnosis

Acute febrile illness with two or more of the following;

• headache,
• retro-orbital pain,
• myalgia,
•  arthralgia/bone pain,
• rash,
• haemorrhagic manifestations,
• leucopenia (WBCs 5000 cells/mm3),
• thrombocytopenia (platelet count <150,000 cells/mm3),
• rising haematocrit (5-10%); and at least one of following:

– supportive serology on single serum sample: titre:2: 1280 with haemagglutination inhibition test, comparable IgG titre with enzyme-linked immunosorbent assay, or testing positive in lgM antibody test, and occurrence at the same location and time as confirmed cases of dengue fever.

Confirmed diagnosis

Probable case with at least one of the following:

– isolation of dengue virus from serum, CSF or autopsy samples.

– fourfold or greater increase in 1>serum lgG (haemagglutination inhibition test) or increase in lgM antibody specific to dengue virus.

– detection of dengue virus or antigen in tissue, serum or cerebrospinal fluid by immune histo chemistry ,immunofluorescence or enzyme-linked immunosorbent assay.

– detection of dengue virus genomic sequences by reverse transcription-polymerase chain reaction

Dengue haemorrhagic fever

All of following:

• acute onset of fever of 2-7 days’ duration.
• haemorrhagic manifestations, shown by any of the following; positive tourniquet test, petechiae, purpura, or bleeding from mucosa, gastrointestinal tract, injection sites, or other locations.
• platelet counts: 100,000 cells/mm3 ·

Clinical management

Grading of the severity of dengue infection

To decide where to treat the patient, it is important to classify the severity of dengue infection. The presence of thrombocytopenia with concurrent haemoconcentration differentiates grade I and grade II DHF from DF.

Guidelines for treatment

A full blood count of the patient should be done at the first visit. A rapidly decreasing platelet count in parallel with a rising haematocrit compared to the baseline is suggestive of progress to the plasma leakage/critical phase of the disease.

1. Management of dengue fever

These are patients who are able to tolerate adequate volumes of oral fluids and pass urine at least once every 6 hours, and do not have any of the warning signs, particularly when fever subsides. Those with stable haematocrit can be sent home after being advised to return to the hospital immediately if they develop any of the warning signs, and to adhere to the following action plan:

1. Encourage intake of oral rehydration solution (ORS), fruit juice and other fluids containing electrolytes and sugar to replace losses from fever and vomiting. Adequate oral fluid intake may be able to reduce thenumber of hospitalizations.

*Caution: fluids containing sugar/glucose may exacerbate hyperglycaemia of physiological stress from dengue and diabetes mellitus.

• Give paracetamol for high fever if the patient is uncomfortable. The interval of paracetamol dosing should not be less than six hours.

• Tepid sponge if the patient still has high fever.

• Do not give aspirin, ibuprofen or other NSAIDs as these drugs may aggravate gastritis or bleeding.

• Instruct the care-givers that the patient should be brought to hospital immediately if any of the following occur; no clinical improvement, deterioration around the time of defervescence, severe abdominal pain, persistent vomiting cold and clammy extremities, lethargy or irritability/ restlessness, bleeding (e.g. black stools or coffee-ground vomiting), not passing urine for more than 4-6 hours.

• Patients who are sent home should be monitored daily by health care providers for temperature pattern, volume of fluid intake and losses, urine output {volume and frequency), warning signs, signs of plasma leakage and bleeding, haematocrit, and white blood cell and platelet counts.

2. Management of DHF (Febrile Phase)

The management of febrile phase is similar to that of DF.

1. Paracetamol is recommended to keep the temperature below39°C.
2. Copious amount of fluid should be given orally, to the extent the patient tolerates, oral rehydration solution (ORS), such as those used for the treatment of diarrhoeal diseases and/or fruit juices are preferable to plain water. IV fluid maybe administered if the patient is vomiting persistently or refusing to feed.

Control measures

1. Mosquito control

The vectors of DF and DHF (e.g., A. aegypti) breed in and around houses and, in principle can be controlled by individual and community action, using anti-adult and anti-larval measures.

2. Vaccines

There is no satisfactory vaccine and no immediate prospect of preventing the disease by immunization.

3. Other measures

Isolation of the patient under bed-nets during the first few days; individual protection against mosquitoes. The personal prophylactic measures are wearing of full sleeves shirts and full pants; use of mosquito repellent creams, liquids, coils, mats etc.; use of bed-nets for sleeping infants and young children during day time to prevent mosquito bite. The environmental measurements are detection and elimination of mosquito breeding places, management of roof tops, porticos and sunshades, proper covering of stored water, observation of weekly dry day.

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Sources: Park, K. (2021). Park’s Textbook of Preventive and Social Medicine (26th ed.). Bhanot Publishers.