Elevated Dengue fever activity reported at Dhaka & Chattogram: Clinical Manifestation and Diagnosis of Dengue Fever

Dengue is endemic in Bangladesh with recurrent outbreaks.  Health officials in Bangladesh have reported elevated dengue fever activity in Bangladesh during 2022. Dhaka and Chattogram has become a hotspot for dengue fever (DF).

Why DF rising in August & September?

       The risk of dengue fever transmission in Bangladesh exists nationwide and year-round; however, the risk is highest during the rainy season, which typically occurs June-September. This year in September dengue hospitalsation double against August figure.

       Dengue totally depends on weather. Several factors such as rainfall, temperature, humidity provide appropriate conditions for its survival, reproduction, breeding, egg hatching and virus transmissibility. 

       The pattern of rainfall changed over the past few years. The expert added that the number of dengue cases usually peaked in July and August, but low rainfall halted the rise in cases and it started going up again due to intermittent rain in the beginning of September.

How many infected and how many deaths?

       According to the Directorate General of Health Services (DGHS), a total of 14,362 people were admitted to hospitals since January this year. A total of 8,181 dengue patients were hospitalised in 26 days of September across the country, which was 57 per cent of the total hospitalisation this year since January.

       A total of 11,071 or over 77 per cent of dengue patients were reported to be hospitalised in Dhaka city and next is Cox’s Bazar.

       The official death toll to 53 across the country this year since January, said a press release of the Directorate General of Health Services. Of the total dengue deaths this year, 26 people died in Dhaka city, 23 in Chattogram and four in Barishal division.

       The data also showed that 70 per cent of the total deaths occurred between age one and 40 years. Experts believed late hospitalisation and lack of prompt treatment for the high number of deaths.  Secondary infections are cause for the majority of the reported deaths up to age 40.

TAKE HOME MESSAGE:

Dengue is the most common mosquito-borne, viral disease in the world. Dengue virus is a single stranded positive polarity RNA virus, belongs to the family Flaviviridae. It is transmitted through the bite of an infected female mosquito of Aedes species.

There are 4 distinct, but closely related, serotypes of the virus (DEN-1, DEN-2, DEN-3 and DEN-4). A fifth addition to the existing serotypes of dengue viruses is the DENV-5, which was announced in October 2013, after its detection in Malaysia.

Recovery from infection by one serotype provides heterotypic or cross-immunity to the other serotypes. This is only partial and temporary, lasts only a few months, but homotype immunity is lifelong.

For this reason, a person can be infected with a dengue virus as many as four times in his or her lifetime. Subsequent infections (secondary infection) by other serotypes increase the risk of developing severe dengue.


Stepwise Approach of Dengue Case Evaluation

Step 1 – Overall assessment

1.1 The history should include:

       Date of onset of fever/illness;

       Quantity of oral fluid intake;

       Diarrhoea;

       Urine output (frequency, volume and time of last voiding);

       Assessment of warning signs ;

       Change in mental state/seizure/dizziness;

       Other important relevant history, such as family or neighbourhood dengue, travel to dengue-endemic areas, co-existing conditions (e.g. infancy, pregnancy, obesity, diabetes mellitus, hypertension), jungle trekking and swimming in waterfalls (consider leptospirosis, typhus, malaria), recent unprotected sex or drug abuse (consider acute HIV-seroconversion illness).

1.2 The physical examination should include

       Assessment of mental state;

       Assessment of hydration status;

       Assessment of haemodynamic status;

       Checking for quiet tachypnoea/acidotic breathing/pleural effusion;

       Checking for abdominal tenderness/hepatomegaly/ascites;

       Examination for rash and bleeding manifestations;

       Tourniquet test (repeat if previously negative or if there is no bleeding manifestation).

1.3 The investigation

• A full blood count (CBC) should be done at the first visit (it may be normal); Platelet count and haematocrit repeated daily until the critical phase is over.

• The haematocrit in the early febrile phase could be used as the patient’s own baseline.

• Decreasing white blood cell and platelet counts make the diagnosis of dengue very likely.

• Leukopenia usually precedes the onset of the critical phase and has been associated with severe disease.

• A rapid decrease in platelet count, concomitant with a rising haematocrit compared to the baseline, is suggestive of progress to the plasma leakage/critical phase of the disease.

• These changes are usually preceded by leukopenia (≤ 5000 cells/mm3). In the absence of the patient’s baseline, age-specific population haematocrit levels could be used as a surrogate during the critical phase.

• If facilities for a full blood count are not available or if resources are limited, such as in outbreak settings, a full blood count or microhaematocrit should be done at the first visit to establish the baseline. This should be repeated after the 3rd day of illness and in those with warning signs and risk factors for severe disease.

• Dengue-specific laboratory tests should be performed to confirm the diagnosis.

However, it is not necessary for the acute management of patients, except in cases with unusual manifestations.

Additional tests should be considered in patients with co-morbidities and severe disease as indicated. These may include tests of liver function, glucose, serum electrolytes, urea and albumin.


Step 2 - Diagnosis, Assessment of disease phase and severity

Diagnosis, assessment of disease phase and severity on the basis of evaluations of the history, physical examination and/or full blood count and haematocrit.

Clinicians should determine whether the disease is dengue, which phase it is in (febrile, critical or recovery), whether there are warning signs, the hydration and haemodynamic state of the patient, and whether the patient requires admission. For blood pressure assessment follow age specific blood pressure chart.

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In most of the cases with dengue virus infection remain asymptomatic; however, it can cause a wide spectrum of clinical manifestations from mild febrile illness with spontaneous recovery to hemorrhagic dengue fever (DF) and/or dengue shock syndrome (DSS).

Dengue virus infections may be asymptomatic or may lead to undifferentiated fever, dengue fever, or dengue haemorrhagic fever (DHF) with plasma leakage that may lead to hypovolaemic shock Dengue Shock Syndrome (DSS).

Many patients infected with dengue virus remain asymptomatic. Others, after an Incubation period of 4-7 (range 3-14) days, develop a febrile illness the manifestations of which are similar and overlapping in nature grouped into ‘Dengue Syndromes’ which encompass the following:

       Undifferentiated fever

       DF

       DHF

·       DSS

       Expanded Dengue Syndrome (rare)

Asymptomatic Infection

The majority of infections in children under age 15 years are asymptomatic or minimally symptomatic.

Symptomatic Infection

Undifferentiated fever

       Those who have been infected with dengue virus, especially for the first time (i.e. primary dengue infection), may develop a simple fever indistinguishable from other viral infections.

       Maculopapular rashes may accompany the fever or may appear during defervescence.

       Upper respiratory and gastrointestinal symptoms are common.

Dengue fever

Typically, the onset of DF is sudden with a sharp rise in temperature and is frequently associated with a flushed face and headache.

Occasionally, chills accompany the sudden rise in temperature.

The following features are usually observed:

       Retro-orbital pain on eye movement or pressure on eye

       Photophobia

       Backache and pain in the muscles and joints/bones.

       The other common symptoms include anorexia and altered taste sensation, constipation, colicky pain and abdominal tenderness.

It is noteworthy that these symptoms and signs of DF vary markedly in frequency and severity.

Fever:

The body temperature is usually between 39°C and 40°C (102°F to 104°F) and the fever may be biphasic, lasting 2-7 days in the majority of cases.

Rash:

• First 2 to 3 days-Diffuse flushing or fleeting eruptions may be seen on the face, neck and chest

• Third and fourth day-a conspicuous rash that may be maculopapular or rubella form

• Afebrile period or defervescence - Petechiae surrounding scattered pale, round areas of normal skin may appear over the dorsum of the feet, on the legs, and on the hands and arms. Skin itching maybe observed.

Hemorrhagic manifestations:

In DF with unusual hemorrhage, Petechiae may be present. Other bleeding such as massive epistaxis, menorrhagia and gastrointestinal bleeding rarely occur in DF, complicated with thrombocytopenia. Tourniquet test will be positive in this case.

Early laboratory confirmation of clinical diagnosis may be important because some patients progress within a short period from mild to severe disease and sometimes to death. Early intervention may be life-saving.

Lab Tests for Diagnosis and Monitoring

The management of DS is based on clinical judgment rather than laboratory evaluations alone.

Dengue Diagnostic Test

Detection of Antigen: NS1 antigen (non-structural protein 1):

       NS1 antigen rapid test- positive within minutes of starting symptoms.

       The ELISA NS1 antigen will be positive on first day of illness.

       This test becomes negative from day 4-5 of illness.

       Commercial kits for the detection of NS1 antigen are now available in ELISA or rapid test format.

Dengue IgM /IgG test (MAC ELISA or Rapid ICT):

       Anti-dengue IgM specific antibodies can be detected after 5 days of the onset of fever and highest level achieved after 7 days.

       It can be detected in low level up to 1-3 months after fever.

       In primary dengue infection- IgM will be more than IgG early period and send IgG at 9 or 10th day of fever.

       Level of this IgG may persist at low levels for decades, indicating past dengue infection.

       In secondary dengue infection- higher elevation of anti-dengue specific IgG antibodies and lower levels of IgM. The higher IgG levels remain for 30–40 days.

       Rapid ICT test provides result within 15 to 20 minutes.

Nucleic Acid Detection:

       The reverse transcriptase polymerase chain reaction (RT-PCR)- confirm diagnosis (<5 days of illness).

       The amplified DEN viral RNAs can be detected either by tradition or real time PCR.

       This test is expensive and available only in referral centers.

However, few indirect tests may be suggestive of DS from the outset. The following tests may be done

1. Complete Blood Count (CBC):

Including Total Leucocyte Count, Total Platelet Count and HcT should be done on first consultation of the patient to have the baseline: Recommendations:

       All febrile patients at the first visit within one week

       All patients with warning signs.

Leucopenia is common in both adults and children with DF and has an important diagnostic implication in early period.

The change in total white cell count (≤5000 cells/mm3) and ratio of neutrophils to lymphocyte (neutrophils

This finding precedes thrombocytopenia or rising haematocrit. These changes seen in DF and DHF.

Thrombocytopenia is observed in some patients with DF. Mild (100,000 to 150,000 cells/mm3) is common and about half of all DF patients have platelet count below 100,000 cells/mm3; A sudden drop in platelet count to below 100,000 occurs before the onset of shock or subsidence of fever. The level of platelet count is correlated with severity of DHF.

Severe thrombocytopenia (<100,000/mm3) usually precedes/accompanies overt plasma leakage.

Haematocrit: A slight increase may be due to high fever, anorexia and vomiting (10%). A sudden rise in haematocrit is observed simultaneously or shortly after the drop in platelet count.

Haemoconcentration or rising haematocrit by 20% from the baseline, e.g. from haematocrit of 35% to ≥42% is objective evidence of leakage of plasma.

It should be noted that the level of haematocrit may be affected by early volume replacement and by bleeding.

2. Biochemical Tests:

Serum AST (SGOT) and ALT (SGPT):

AST and ALT levels are frequently elevated in both adults and children with DF and DHF; AST and ALT Levels are significantly higher (5 to 15 times the upper limit of normal) in patients with DHF. Commonly AST is more than ALT in these cases.

Haematocrit and Complete blood count if the patient presented within 3 days of fever.

Follow up testing may be done on 1st afebrile day, but should be done daily once DHF is suspected.

A regular haematocrit is more important for management than the thrombocytopenia.

Even in severe dengue especially with shock) hourly haematocrit is crucial for management.

Once the platelet count begins to rise and reaches ≥ 50,000/mm3, daily lab evaluations may be discontinued.

In Special Cases:

       Hypoproteinemia/Hypoalbuminaemia (as a consequence of plasma leakage).

       Hyponatremia is frequently observed in DHF and is more severe in shock.

       Hypocalcemia (corrected for hypoalbuminemia) has been observed in DHF.

       Metabolic acidosis is frequently found in cases with prolonged shock.

       Blood urea nitrogen is elevated in prolonged shock.

3. Coagulation Profile:

       Assays of coagulation and fibrinolytic factors show reduction in DSS cases.

       Partial thromboplastin time and prothrombin time are prolonged in about half and one third of DHF cases respectively.

       Thrombin time is also prolonged in severe cases.

4. Other tests:

       Urine R/M/E: Albuminuria

       Stool test: Occult blood is often found in the stool.

       Chest X-Ray or Ultrasonography: For detection of pleural effusions or ascites.

       Other tests for exclusion: Malaria (MP/ICT), Enteric fever (Blood culture) may be required for patients with compatible clinical syndromes.

       Other test as and when clinically indicated (especially for Dengue expanded syndrome): Serum Albumin, Liver Function Tests, Renal Function test, Serum electrolytes, Imaging, ECG, Echocardiography, and CSF etc.

Read In Details


https://www.newagebd.net/article/182115/57pc-dengue-hospitalisation-in-past-26-days
https://iedcr.gov.bd/nbph/issue-sections/19a3a15a-b231-48cc-9d8f-dc20d577365b
https://old.dghs.gov.bd/images/docs/vpr/Revised_National_Guideline_for_Clinical_Management_of_Dengue_Syndrome_2018.pdf
https://www.newagebd.net/article/181752/dengue-cases-keep-rising-alarmingly

This is for informational purposes only. You should consult your clinical textbook for advising your patients.