Dengue is a viral infection that is transmitted by mosquitoes in tropical areas. According to WHO, Dengue fever is considered as the second most important tropical disease next to Malaria. South Asia has the highest burden, of which India is one of the countries maximally affected by it.
All the four serotypes of Dengue virus are endemic in India. Asymptomatic infections are much more frequent than symptomatic ones. Infection with one serotype of Dengue does not confer cross protection against other serotype. On subsequent infection, it may lead to serious forms of the disease like Dengue Hemorrhagic Fever and Dengue Shock Syndrome. Considering this, it becomes very important to distinguish primary from secondary dengue, early in the course of infection. It helps in predicting prognosis and also in deciding about whether a patient needs hospitalization/close monitoring or could be managed at home. This is especially important during epidemics and outbreaks.
Serological markers of Dengue infection
Dengue viraemia is universal in febrile patients with dengue; Dengue NS1 Ag occurs prior to the onset of fever/symptoms and peaks 2-3 days after the onset of illness. Serologically, a primary dengue infection results in detectable levels of IgM antibodies by the 3rd afebrile day after infection, which generally persist for 2-6 months. Dengue IgG antibodies appear after IgM, approximately at the day 7 of the fever, in the primary infection and persist for a longer time, even up to years. Secondary Dengue infections are characterized by a rapid increase in IgG levels, with modest increases in IgM.
The following table summarizes results that may be seen with antibody testing:
|Low or negative or not tested
||Four-fold increase in samples taken 2-4 weeks part
|Low or negative
||Too soon after initial exposure for antibodies to develop or symptoms due to another cause
Positive IgM and IgG tests for Dengue antibodies detected in a sample means that the patient became infected with dengue virus within recent weeks.
IgG as a sero-marker of Dengue infection.
If the IgG is positive but the IgM is low or negative, then it is likely that the patient had an infection sometime in the past. Presence of IgG alone (absence of NS1 Ag and/or IgM), does not indicate active dengue infection. Test results, therefore, should be used in conjunction with clinical evaluation, including exposure history and clinical symptoms.
Among the two antibodies, IgG is a less reliable marker in the diagnosis of Dengue infection. The picture of only IgG reactive status can occur in a patient with past dengue infection or who currently has some other fever, like enteric fever, UTI, or other flaviviral infections. Even healthy people in endemic areas may have detectable serum IgG antibodies because of the bites from infected mosquitoes.
False-positive anti-Dengue IgG test results have been documented in patients with bacteremia, leptospirosis, Q fever and other viral infections like Chikangunya, Tick-borne Encephalitis, Varicella, Cytomegalovirus and Epstein-Barr infections.
The following points should be considered by the clinicians before categorizing only IgG-Dengue-positives as Dengue fever patients.
- Clinical presentation
- Clinical evidence of plasma leakage
- Laboratory tests (raised alanine transaminase and aspartate transaminase within 2-3 times normal limits, mildly decreased total protein and albumin)
- Radiological evidence of plasma leakage
- and gall bladder wall changes on ultrasonography.
- Shiv Sekhar Chatterjee, Ankush Sharma, Shilpee Choudhary, Sushil Kumar Chumber, et al. Significance of IgG optical density ratios (index value) in single reactive anti-Dengue virus IgG capture ELISA. Iranian Journal of Microbiology. Vol.8 No.6 Dec’16:395-400.
- Dr. P.Malini, Dr. M.Sumathi, Dr. T.Ravikumar. Categorization of Dengue based on duration of fever and serological markers in a tertiary care hospital. Indian Journal of Basic and Applied Medical Research; Jun’17: Vol.8, Issue-3, 409-413.
- GS Ajantha, PA Jain, AS Kalabhavi, RD Kulkarni, SS Patil, PC Shetty, RM Shubhada, AK Upadhya. Association of platelet count and serological markers of dengue infection- importance of NS1 antigen. Indian Journal of Medical Microbiology, Vol. 29, No. 4, October-December, 2011, pp. 359-362.