DENGUE INFECTION

DENGUE IS CLASSIFIED INTO PRIMARY AND SECONDARY INFECTIONS

When a person gets infected with Dengue for the first time with a certain serotype of the virus – the infection is labelled as primary dengue
When the same individual is again infected by the dengue virus, but by a serotype other than the one which caused the initial infection – this is called secondary dengue
There are four virus serotypes which are designated as DEN-1, DEN-2, DEN-3 and DEN-4.
At present DEN1 and DEN2 serotypes are widespread in India.

CLINICAL AND PATHOLOGICAL DIFFERENCES BETWEEN PRIMARY AND SECONDARY DENGUE

Clinical Differences

Primary infection is milder in intensity and presents generally with coryza, fever, rash, body ache, joint ache and headache, chills and malaise
Secondary infection presents a much more serious clinical course comprising Grade 3 dengue hemorrhagic fever and complications like dengue shock syndrome

Serological Differences

Serologically, primary infection is characterized by rise in dengue-specific IgM by 4–5 days of fever onset, followed by rise of IgG antibody with 7–10 days.
IgM antibodies for dengue may remain elevated for 2 to 3 months after the illness.
The diagnosis of primary dengue in the initial 5 days, therefore, requires utilization of polymerase chain reaction techniques (RT-PCR) or antigen detection, especially the NS1 antigen
Secondary infection is recognized by an early rise in the IgG antibody titer and a lower titer of IgM rise.
Again, early phases of secondary dengue also show PCR and NS1 positivity

Ref: Mandavdhare HS, Sharma V. Differentiating primary and secondary dengue infections: Why and how? Med J DY PatilUniv 2016;9:594-5

	IgG antibody	IgM antibody	NS1 antigen	Polymerase chain reaction
Early primary infection	–	–	+++	+++
Late primary infection	-/+	++	–	–
Early primary infection	++	-/+	++	+++
Late primary infection	++	+	–	–

* – Likely to be negative, + Likely to positive, +/- Varibale, ++ very likely to be positive, +++ Extremely likely to be positive

Ref: Center for Disease Control and Prevention. Laboratory Guidance and Diagnostic

Testing. Available from: http://www.cdc.gov/dengue/clinicallab/laboratory.html

Cross Reactivity in Serology needs to be factored in prior to a diagnosis

Serological cross-reactivity across the flavivirus group is common (i.e. between dengue 1, 2, 3 & 4, Japanese encephalitis, Murray Valley encephalitis, St. Louis encephalitis, West Nile, and yellow fever viruses). These diseases must be excluded before confirmation of diagnosis.
Heterophilic antibodies are a well-recognised cause of interference in immunoassays . These antibodies to animal IgG may cross-react with reagent antibodies and generate a false positive signal. This must be excluded before confirmation of diagnosis.
Cross reactivity is also known due to interference with antibodies against Epstein-Barr virus, Malarial parasite, Influenza A and B, Anti-nuclear antibody, Rheumatoid factor Hepatitis A, Leptospira, Salmonella typhi, Scrub typhus and West Nile virus

Ref: WHO Report: Evaluation of commercially available anti-dengue virus IgM tests.

Diagnostic evaluation series No.3

HEALTH AUTHORITIES STRONGLY DISCOURAGE RAPID DENGUE TESTS

The use of rapid tests for dengue has been discouraged by the Health Ministry of India as the rapid diagnostic kits are generating up to 50% of false ‘positives’ for dengue (Times of India report, Sep 17, 2015)

PCR OFFFERS A CLEAR ADVANTAGE OVER OTHER MODALITIES IN DIAGNOSING DENGUE

Infection	Sensitivity
Infection	RT – PCR	NS1	Clinical Benefit
Primary	95%	90%	↑5%
Secondary	95%	85%	↑10%

Additional 5-10% patients accurately detected positive by PCR

Ref: Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control:

New Edition- WHO 2009.ECDC training Workshop on laboratory diagnosis of dengue

virus infections Berlin, 23-27 January 2012. CENTER FOR DISEASE CONTROL

WHICH INFORMATION DOES THE LABORATORY NEED FOR FURTHER INTERPRETATION OF THE RESULTS?

The availability of the following data points pertaining to the Clinical and personal history of the patient could prove instrumental in corroborating the lab test results with the clinical presentation

Mandatory:

Date of onset of illness ( not fever alone )
Date of sample collection
Travel history (country, dates…)

DENGUE IS OFTEN SUBCLINICAL!

Quite a large proportion of patients who test positive for Dengue infection, do not show any symptoms.

In case of elevated IgG and IgM with no symptoms (seropositive but asymptomatic) – it could be the convalescent phase of the disease as antibodies can be found for upto 3 months after the illness

This is in fact the “Unapparent” or “Subclinical” form of Dengue which forms a large portion of the total disease burden

The WHO’s regional office for South East Asia confirms the following

There are many people who are infected with the virus and do not suffer from any signs or symptoms of the disease. For every patient with symptoms and signs, there may be four or five persons with either no symptoms or very mild symptoms.

Ref: http://www.searo.who.int/srilanka/areas/dengue/faqs-on-dengue.pdf?ua=1

https://www.cdc.gov/dengue/clinicallab/laboratory.html