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 ~  Abstract
 ~ Introduction
 ~  Materials and Me...
 ~ Results
 ~ Discussion
 ~ Acknowledgments
 ~  References
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BRIEF COMMUNICATION
Year : 2012  |  Volume : 30  |  Issue : 2  |  Page : 222-226
 

Awareness of changing trends in epidemiology of dengue fever is essential for epidemiological surveillance


Department of Microbiology, Maulana Azad Medical College, New Delhi, India

Date of Submission07-May-2011
Date of Acceptance12-Sep-2011
Date of Web Publication28-May-2012

Correspondence Address:
M Matlani
Department of Microbiology, Maulana Azad Medical College, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0255-0857.96699

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 ~ Abstract 

Dengue has become endemic in India with outbreaks occurring almost every year. The seroprevalence and serotypic data of the last 7 years in samples obtained from suspected dengue patients from a tertiary care hospital were analyzed. Out of 7846 serum samples received in the virology laboratory from suspected dengue cases during 2002 to 2008, 2366 (30.15%) were serologically confirmed. Serotyping was done using mRT-PCR. All the four serotypes were detected in 2003, while data in 2004, 2005 and 2006 revealed the the predominance of Den-3. In the year 2007 predominance of Den-2 was observed, whereas in 2008 Den-1 was the most common serotype isolated. Overall, Den-2 and Den-3 were the most predominant serotypes during 2003-2007 but Den-1 replaced these strains in the year 2008. Since the emergence of a new predominant strain can lead to the occurrence of an outbreak, presence of Den-1 in the year 2008 would pose an alarming situation before us. Well-targeted population-based epidemiological studies are urgently required to control dengue menace.


Keywords: Dengue, epidemiology, serotypes


How to cite this article:
Chakravarti A, Matlani M, Kashyap B, Kumar A. Awareness of changing trends in epidemiology of dengue fever is essential for epidemiological surveillance. Indian J Med Microbiol 2012;30:222-6

How to cite this URL:
Chakravarti A, Matlani M, Kashyap B, Kumar A. Awareness of changing trends in epidemiology of dengue fever is essential for epidemiological surveillance. Indian J Med Microbiol [serial online] 2012 [cited 2019 Jun 26];30:222-6. Available from: http://www.ijmm.org/text.asp?2012/30/2/222/96699



 ~ Introduction Top


Dengue is the most important arthropod-borne viral disease of public health significance, the global prevalence of which has grown dramatically in recent decades with estimated 2.5 billion people at a risk of acquiring dengue viral infection and more than 50 million new infections being projected annually. [1],[2] Dengue and its severe manifestations: DHF and dengue shock syndrome (DSS), are recognized as important emerging public health problems in tropics and subtropics.

Dengue fever and DHF/DSS are caused by the four viral serotypes transmitted from viraemic to susceptible humans mainly by bites of Aedes aegypti and Aedes albopictus mosquito species. Recovery from infection by one serotype provides lifelong immunity against that particular serotype but imparts only partial immunity against subsequent infection by other three serotypes. [1],[2] Dengue is one of the notable viral infections, the global epidemiology of which has changed dramatically in recent years and the Indian encounter with this disease is intriguing. Dengue infection has been known to be endemic in many parts of India for over two centuries as a benign and self limited disease and outbreaks have been reported at regular intervals from almost all parts of India. Delhi has become hyperendemic for dengue with outbreaks occurring frequently, the last reported in 2006. [2],[3] Epidemiology of dengue infection in Delhi is rapidly changing with increasing frequency of outbreaks. All the four serotypes have been reported to be circulating in this region with changes occurring in the leading serotypes. Since there is no vaccine available for the DF, the prevention and control of the disease mainly depends upon the epidemiological surveillance that provides reliable estimate of the disease and thereby helping to implement effective vector control measures. It is of utmost importance to characterize the circulating serotypes of dengue virus in our community and understand the evolutionary processes influencing the dengue virus. This retrospective study was planned to review the changing epidemiology of the disease by analyzing the predominantly circulating serotypes from the suspected cases of dengue presenting to our hospital between the years 2002 and 2008.


 ~ Materials and Methods Top


Specimens

A total number of 7846 acute phase blood samples were collected from clinically suspected cases of dengue virus infection, coming to the various outpatient departments, emergency services and admitted patients in our Hospital, over a period of 7 years. WHO criteria were followed for inclusion or exclusion of a case of dengue infection and their categorization as DF/DHF. [4] All the samples were tested for the presence of anti-dengue IgM using MAC ELISA, developed and commercialized by NIV (National Institute of Virology), Pune, [5] and recommended by National Vector Borne Disease control programme. Samples obtained in early phase (within 5 days of illness) (n=610) were tested for dengue viral RNA using RT-PCR and serotyped by type-specific multiplex PCR as per the modified method of Harris et al. published previously. [6],[7] Statistical analysis was done by using SPSS version 12.


 ~ Results Top


During the study period (2002-2008), a total of 7846 serum samples were tested for dengue IgM and IgG antibodies. Year wise distribution of the number of tested samples being 82 in 2002, 1550 in 2003, 444 in 2004, 583 in 2005, 3388 in 2006, 645 in 2007 and 1154 in the year 2008. Of these, 2366 (30.15%) were positive for dengue-specific IgM antibodies. A maximum number of seropositive cases (1107) were detected in the year 2006, followed by 580 cases in the year 2003. Year-wise distribution of samples positive for dengue IgM and IgG antibodies is shown in [Table 1]. Six hundred and ten samples which were obtained within 5 days of illness during the study period were tested for the presence of viral RNA by RT-PCR. A total of 125 samples demonstrated the viral RNA. [Figure 1] depicts the year wise distribution of samples positive for dengue viral RNA. Year-wise distribution of dengue virus serotype among the patients has been shown in [Figure 2]. Den-2 was the predominant serotype in the year 2002. All four serotypes of dengue -1, 2, 3, 4 were co-circulating in 2003 and amongst them Den-2 was the most common. This was followed by predominance of Den-3 during 2004, 2005 and 2006. However, in the year 2007, all four serotypes were identified. In 2008, Den-1 replaced Den-2 and Den-3 which were predominant serotypes in last few years. All four serotypes were present in 2003 and 2007 but co-infection of more than one dengue serotypes (Den-2 and Den-3) was detected in one patient during the year 2007. On the basis of clinical findings recorded in the patient information sheet and the other laboratory findings, the 125 viral RNA positive patients were categorized as DF and DHF. Seventy-four patients were categorized as DF and 51 as having DHF (as per WHO guidelines). Further analysis on the basis of disease severity revealed that Den-3 was the most predominant serotype amongst the DF group, while Den-2 was found to be the major causative type amongst DHF group [Table 2].
Figure 1: Year-wise distribution of RNA-positive samples

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Figure 2: Year-wise data of dengue serotypes detected

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Table 1: Demographic and serologic profi le of dengue patients

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Table 2: Distribution of DF and DHF among the four serotypes

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The disease was present in all age groups of study population; however predominance of adult population was noted. Den-2 was the major causative agent in children. On the other hand, Den-3 was the predominant serotype in adults. Male predominance was seen in during all 7 years. Den-3 was found to be the most common serotype in both the genders followed by Den-2. [Figure 3] and [Figure 4].
Figure 3: Sex-wise distribution of dengue serotypes amongst Rt-PCR-positive cases

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Figure 4: Age-wise distribution of dengue serotypes among adult and paediatric patients

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 ~ Discussion Top


Dengue is one of the major re-emerging viral infections. There has been a considerable increase in the geographic spread, number of cases and severity of the disease in the past four decades, since there is a drastic change in the environment due to rapid urbanization and increase in transportation facilities in several parts of India. Our hospital is a 1690-bedded tertiary care hospital with thickly populated catchment areas. Being a dengue sero surveillance centre, a large number of samples are obtained in this hospital. Hence, the serotypic data from these samples may reflect the circulating serotype in Delhi and adjoining areas and may help to develop effective control and management strategies against this impeding dengue menace. DF has been known to be endemic in India for more than 20 years as a benign and self-limited disease; however, during recent years, the severe form as DHF is manifesting more frequently. Outbreaks of dengue fever are reported almost every year in India. The first serotype isolated in India was Den-1 in the year 1945 from Kolkata. However, large and severe outbreaks in India have been mostly caused by dengue virus type-2. [1],[8] Delhi has had outbreaks of dengue caused by various dengue virus types in 1967, 1970, 1982, 1988 and 1996. [9] Dengue virus types 1, 2 and 3 have all been isolated during previous dengue outbreaks in Delhi, but a particular type has always predominated. One of the largest outbreaks of DHF/DSS in North India occurred in Delhi and adjoining areas in the year 1996 and the predominant circulating serotype was found to be Den-2 virus. [8],[10],[11] In the post epidemic period, in 1997, circulation of dengue-1 virus was observed in Delhi. [12] The activity of dengue virus was low after 1996 epidemic for 6 years till an upsurge occurred during the 2003 outbreak. In the year 2003 we and the other studies reported on co circulation of all four serotypes for the first time from Delhi. Amongst all the serotypes, Den-2 was the most common circulating serotype, [7],[12] whereas Den-3 was the predominant strain in some other parts of the country. [13] This outbreak was milder than the 1996 outbreak, with most patients presenting with uncomplicated dengue fever, and only a few with DHF/DSS. However, the emergence of a newer dengue serotype after an interval always leads to a major outbreak, which is a matter of concern. During the following years 2004 and 2005, no outbreak was reported but amongst the isolated serotypes in our set up, Den-3 was found to be predominant. In the year 2006, Delhi was again hit by an outbreak due to multiple circulating serotypes, during which Den-3 was found to be the most common circulating serotype. [14] These findings indicate replacement of the earlier circulating serotype Den-2 with Den-3. This shift could have lead to an increased no. of dengue cases in the year 2006. We observed co-circulation of all four serotypes in the year 2007, indicating continuous co-circulation of all four serotypes in Delhi leading to hyperendemicity of dengue in this region. This may also explain the co-infection of multiple serotypes in various cases reported earlier. [14] However, we observed co-infection of Den -2 and Den-3 serotypes in only one patient in the year 2007. During the year 2008, we observed that Den-1 was the most common circulating serotype. Hence, during the year 2008, Den-1 replaced Den-2 and Den-3 to establish itself as the predominant strain in Delhi, 2 years after 2006 outbreak.

Den-1 has been previously reported to be the predominant serotype in post-epidemic periods like in the year 1997 after 1996 outbreak and in 2004 after 2003 outbreak. [11] The emergence of a newer dengue serotype after a long period has always lead to major outbreaks, which is a matter of concern. [13],[14] Hence, it may be predicted that after Den-3 and Den-2 having caused major outbreaks Den-1 could become the predominant strain causing the outbreaks in future. The trend for the increased incidence of dengue infection among young adults has been observed in previous studies [15] and has important implications for control and prevention. Den-3 was the major circulating serotype in children, while Den-2 was the predominant one in adults. However, predominance of any serotype in either children or adults was not significant (P value=0.46). Den-2 was found to be the most common serotype in both the genders, and gender-based predominance of any serotype could not be established. It has been earlier established that in many of the Asian communities, lower disease incidence in women may be a statistical artefact related to lower reporting and care-seeking for women and that determining sex differences, both in infection and severity of disease, requires well-designed and targeted studies to confine both biological and social factors that confer disease patterns in a community.

On analyzing the disease severity associated with the serotypes, throughout the study period of 7 years, Den-3 was the most predominant serotype amongst the DF group, while Den-2 was found to be the major causative type amongst DHF group. The association of Den-3 with DF and Den-2 with DHF was seen in a significant number of cases.

Previous studies have also suggested that Den-2 causes more sever disease than the other serotypes, while Den-1 was thought to be associated with mild a form of the disease. [16],[17] However, in the year 2008, Den-1 was found to be the predominant serotype causing both DHF as well as in DF, whereas Den-2 and Den-3 were isolated from fewer patients. During the year 2008, 60% (12/20) cases due to Den-1 had DHF (data published previously), [18] whereas during previous years only 30% (3/10) Den-1 had DHF. This increase in DHF cases due to Den-1 might be due to the heterologous infection leading to ADE (antibody dependant enhancement) resulting imbalance of the levels of cytokines, or due to some unknown genetic changes in the circulating strain which could led to increased virulence of the particular strain. [17],[18] Hence, it would be important to study the differential pathogenicity amongst the dengue serotypes. The present study highlights the emergence of Den-1 as the predominant serotype in Delhi in the year 2008. Our finding of two or more serotypes co-circulating every year during the study period highlights the extent of hyperendemincity of dengue serotypes in this region. Presently, changing characteristics of the disease require grim research attention. Currently, there are no licensed vaccines for dengue, and promising candidates are progressing through clinical trials. Moreover, there is no specific drug available and treatment is only supportive. Hence, the containment of spread of the vector and the disease is still extremely important. The data on serotypes is very important as this will help to develop improved, proactive, laboratory-based surveillance systems that can predict impending dengue outbreak. Such predictions will help to initiate the preventive and control measures well in time for the containment of spread of the disease.

At present, dengue control and prevention require awareness of factors beyond those commonly seen in tropical countries. Many of the affected countries are poor and developing. Realistic approaches for their infrastructure are required to be urgently developed. [15] Detailed serological and virological studies of dengue outbreaks in endemic areas are required to pinpoint the nature of the outbreaks to help to develop effective control measures. Well-targeted population-based epidemiological studies with clear operational objectives are urgently required to control high morbidity and mortality due to dengue.


 ~ Acknowledgments Top


We thankfully acknowledge the financial assistance provided to us by the Department of science and technology, for conducting this research work.

 
 ~ References Top

1.Guzman MG, Kouri G. Dengue diagnosis, advances and challenges. Int J Infect Dis 2004;8:69-80.  Back to cited text no. 1
    
2.Chakravarti A, Kumaria R. Eco-epidemiological analysis of dengue infection during an outbreak of dengue fever, India. Virol J 2005;2:32.  Back to cited text no. 2
    
3.Gupta E, Dar L, Narang P, Srivastava VK, Broor S. Serodiagnosis of dengue during outbreak at a tertiary care hospital in Delhi. Indian J Med Res 2005;121:36-8.  Back to cited text no. 3
    
4.World Health Organization. Clinical diagnosis. In: Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control. 2 nd ed. Geneva: WHO; 1997. p. 12-23.  Back to cited text no. 4
    
5.Sathish N, Manayani DJ, Shankar V, Abraham M, Nithyanandam G, Sridharan G. Comparison of IgM capture ELISA with a commercial rapid immunochromatographic card test and IgM microwell ELISA for the detection of antibodies to dengue viruses. Indian J Med Res 2002;115:31-6.  Back to cited text no. 5
    
6.Harris E, Roberts TG, Smith L, Selle J, Kramer LD, Valle S, et al. Typing of dengue viruses in clinical specimens and mosquitoes by single-tube multiplex reverse transcriptase PCR. J Clin Microbiol 1998;36:2634-9.  Back to cited text no. 6
    
7.Kumaria R, Chakravarti A. Molecular detection and serotypic characterization of dengue viruses by single-tube multiplex reverse transcriptase-polymerase chain reaction. Diagn Microbiol Infect Dis 2005;52:311-6.  Back to cited text no. 7
    
8.Dash PK, Parida MM, Saxena P. Reemergence of dengue virus type-3 (subtype-III) in India: Implications for increased incidence of DHF and DSS. Virol J 2006;3:55.  Back to cited text no. 8
    
9.Dar L, Gupta E, Narang P, Broor S. Cocirculation of Dengue Serotypes, Delhi, India, 2003. Emerg Infect Dis 2006;12:352-3.  Back to cited text no. 9
    
10.Broor S, Dar L, Sengupta S, Chakaraborty M, Wali JP, Biswas A, et al. Recent dengue epidemic in Delhi, India. In: Saluzzo JF, Dodet B, editors. Factors in the emergence of arboviruses diseases. Paris: Elsevier; 1997. p. 123-7.  Back to cited text no. 10
    
11.Dar L, Broor S, Sengupta S, Xess I, Seth P. The first major outbreak of dengue hemorrhagic fever in Delhi, India. Emerg Infect Dis 1999;5:589-90.  Back to cited text no. 11
    
12.Gupta E, Dar L, Kapoor G, Broor S. The changing epidemiology of dengue in Delhi, India. Virol J 2006;3:92.  Back to cited text no. 12
    
13.Chaturvedi UC, Nagar R. Dengue and dengue haemorrhagic fever: Indian perspective. J Biosci 2008;33:429-41.  Back to cited text no. 13
    
14.Bharaj P, Chahar HS, Pandey A, Diddi K, Dar L, Guleria R, et al. Concurrent infections by all four dengue virus serotypes during an outbreak of dengue in 2006 in Delhi, India. Virol J 2008;5:1.  Back to cited text no. 14
    
15.Guha-Sapir D, Schimmer B. Dengue fever: New paradigms for a changing epidemiology. Emerg Themes Epidemiol 2005;2:1.  Back to cited text no. 15
    
16.Kalayanarooj S, Nimmannitya S. Clinical and Laboratory Presentations of Dengue Patients with Different Serotypes. Dengue Bull 2000;23:283-7.  Back to cited text no. 16
    
17.Nisalak A, Timothy PE, Nimmannitya S. Serotype-Specific Dengue Virus Circulation And Dengue Disease In Bangkok, Thailand From 1973 To 1999. J Trop Med Hyg 2003;68:191-202.  Back to cited text no. 17
    
18.Chakravarti A, Kumar A, Matlani M. Displacement of dengue virus type 3 and type 2 by dengue virus type 1 in Delhi during 2008. Indian J Med Microbiol 2010;28:412.  Back to cited text no. 18
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