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  Table of Contents    
ORIGINAL ARTICLE  
Year : 2015  |  Volume : 58  |  Issue : 3  |  Page : 328-331
Dengue virus infection: Need for appropriate laboratory tests for diagnosis and management of the condition in children during an outbreak


Department of Microbiology, Pondicherry Institute of Medical Sciences, Kalapet, Puducherry, India

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Date of Web Publication14-Aug-2015
 

   Abstract 

Background: Outbreaks of dengue infection occur in several parts of India with clockwork precision closely related to changing seasons. Most recent outbreak in Puducherry occurred between October 2012 and January 2013, affected a sizable pediatric population. A prospective study was done to characterize the demographic, diagnostic and clinical profile of pediatric patients in a tertiary care center in Puducherry. Materials and Methods: Data of patients serologically positive for either dengue NS1 antigen or anti-dengue IgM antibodies were analyzed. Duration of fever, platelet count, complications, risk factors, morbidity and mortality were analyzed. Results: Among pediatric cases with fever who were screened for NS1/IgM antibody during the recent outbreak, 161 (37.5%) tested positive. NS1 was detected in 85% while 5.5% tested positive for IgM and 3% for IgG. Few (4.9%) tested positive for both NS1 and IgM and 1.2% were positive for both NS1 and IgG. The mean age was 6 years of which 9% were <1-year, the youngest being 1-month old infant. Mean duration of fever was 4 days. Vomiting was associated in 42% of cases. Thrombocytopenia (51%) and hepatomegaly (41%) were two major observations. Among the NS1 positive cases, 49% had thrombocytopenia. IgM alone and NS1 with IgM were associated with thrombocytopenia in 67% and 78% respectively. 14 children had complications of dengue shock syndrome, and four had dengue hemorrhagic fever. Totally, 22 of the children had platelet transfusion. There was no mortality reported among any of these children. Conclusion: Combination of clinical findings and rapid NS1, IgM detection helped in confirming the diagnosis for appropriate management of dengue in children.

Keywords: Dengue fever, NS1 Ag, pediatric cases

How to cite this article:
Palanivel H, Nair S, Subramaniyan A, Ratnam PJ, Kanungo R. Dengue virus infection: Need for appropriate laboratory tests for diagnosis and management of the condition in children during an outbreak. Indian J Pathol Microbiol 2015;58:328-31

How to cite this URL:
Palanivel H, Nair S, Subramaniyan A, Ratnam PJ, Kanungo R. Dengue virus infection: Need for appropriate laboratory tests for diagnosis and management of the condition in children during an outbreak. Indian J Pathol Microbiol [serial online] 2015 [cited 2019 Oct 23];58:328-31. Available from: http://www.ijpmonline.org/text.asp?2015/58/3/328/162865



   Introduction Top


Dengue is a major challenge to public health, especially in South-East Asia. [1] It has a wide geographical distribution and can present with a diverse clinical spectrum. [2] It has been estimated that at least 2.5 billion people worldwide live in areas where there is a significant risk of infection by the dengue virus. [3] Infection with the virus can cause a spectrum of illnesses including relatively mild disease with fever, known as classic dengue fever (DF) and more severe forms such as dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) and less frequently acute hepatitis, disseminated intravascular coagulation, encephalopathy, myocarditis, acute renal failure and hemolytic uremic syndrome both in adults and children. [3] Fever, hepatomegaly, and rashes are common in infants, whereas edema of the lower extremities, retro orbital puffiness, vomiting and convulsions are common manifestations in children. [4]

Estimates suggest that annually over 50 million cases of DHF occur in Asian countries. Global incidence of DF and DHF has increased dramatically in the recent decades. In India, epidemics are becoming more frequent. [5],[6] Involvement of younger age group with increasing frequency in epidemics are indicators of higher incidence of infection. [5],[7] If untreated, mortality from complications of DF is as high as 20%, whereas early case detection and management, decreases mortality to <1%, especially in children. [6],[8] Dengue specific IgM and IgG ELISA are widely used for diagnosis and exposure to dengue respectively.

Dengue in infancy has also been reported from India and Sri Lanka. [9],[10] During an epidemic in 2005-2006, 81 children with DHF were hospitalized in the Pediatric department of Dayanand Medical College and Hospital, Ludhiana, India. [4] During a recent dengue outbreak in Chennai, Tamil Nadu, 20% of total dengue virus infections were detected in infants albeit with low mortality rates. [11] Most recent outbreak in Tamil Nadu and Puducherry occurred during October 2012 to December 2012.

This study was undertaken to correlate NS1 and IgM detection with clinical spectrum of dengue virus infection among the pediatric inpatients with a view to assess the role of these tests in predicting the outcome


   Materials and Methods Top


This descriptive study was done on all serologically confirmed 161 cases of Pediatric dengue (Below 14 years) admitted in a tertiary care center during the outbreak from October to December 2012. All serologically confirmed (NS1 antigen, IgM and IgG antibody positive) pediatric dengue cases admitted in the hospital during the outbreak were included in the study. All adults above 14 years with dengue infection and all children below 14 years with other febrile illness were excluded from the study.

NS1 antigen, anti-dengue IgM/IgG antibodies were detected by rapid immuno-chromatographic method (J. Mitra, Okhla Industrial area, New Delhi, India) as per WHO guidelines. Briefly, 100 μL and 10 μL of patient's serum sample was added to the sample well of NS1 and IgM/IgG device respectively, at room temperature. Appearance of control and test bands were considered positive and reading was taken within 20 min. Data of all 161 pediatric patients serologically positive for either dengue NS1 antigen or anti-dengue IgM/IgG antibodies during the outbreak were analyzed for duration of fever, platelet count, complications if any, associated risk factors, morbidity and mortality. Comparison of various dengue specific parameters with duration of fever and platelet count was done.

Descriptive statistics as frequencies and percentages, confidence intervals (CIs) and Chi-square analysis to identify any association with risk factors and dengue. Any P < 0.05 was considered as statistically significant.


   Results Top


Of the 429 pediatric patients with suspected dengue infection, 161 (38%) were serologically positive for either dengue NS1 antigen or anti-dengue IgM/IgG antibodies. About 68% were in the age group of 5-13 years followed by 29% in 1-5 years and 3% of the patients were below 1-year. Male children accounted for 52% of the infections while remaining were females. Minimum age at which dengue NS1 antigen detected was in a 6 months old child.

Fever was the main clinical presentation in all children. Vomiting was noted in 72 out of 161 (45%), hepatomegaly in 66 (41%) and headache in 28 (17%) children. Abdominal pain was an accompanying feature in 10% of the children. [Table 1] shows the major clinical manifestations in dengue among pediatric age group.
Table 1: Major clinical manifestations in dengue among pediatric age group


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Among the 429 serum samples from the children, 85% (95% CI = 78, 92) were exclusively positive for NS1 antigen, 6% (95% CI = 1, 11) were positive for IgM antibodies and only 3% (95% CI = 0, 6) tested positive for IgG antibodies. A combination of NS1 antigen and IgM were detected in 4.9% while NS1 with IgG was detected in 1.2% of the cases. Few cases (0.6%) tested positive for all three parameters (i.e., NS1, IgM and IgG). [Figure 1] shows the comparison of various dengue specific parameters in the diagnosis of infection.
Figure 1: Comparison of various dengue specific parameters in the diagnosis of infection


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Fourteen children had complications of DSS, and four had DHF. Totally, 24 children had to be transfused with platelets among and 21 of them were positive for NS1 antigen. There was no mortality reported among any of these children.


   Discussion Top


Diagnosing sporadic cases of dengue infection in an infant or very young child is a challenge to the pediatrician in the absence of characteristic clinical symptoms. However, during an outbreak, the infection should be ruled out in all children presenting with fever to any health care facility [12] . In the latest epidemic from October to December 2012, a high incidence of dengue was observed among pediatric patients as compared to the previous epidemics. Among 429 pediatric cases with febrile illness, admitted to this hospital, 37.5% were confirmed to have dengue, making it one of the major causes of hospitalization for febrile illness in children. Older children (5-13 years) were affected more than the younger children. Predominant clinical features reported from several outbreak studies have shown high-grade fever with vomiting, headache and abdominal pain to be the common features that were similar to the present study [13],[14],[15] . An additional feature in the present study was bleeding manifestations, such as nasal bleeding, conjunctival hemorrhage, petechiae and hematemesis which were seen in 9% of cases, a finding similar to a study by Aggarwal et al. [9]

The combination of clinical findings with rapid NS1 and IgM detection helped in confirming the diagnosis. The NS1 antigen was detected as early as the 1 st day of fever with a detection limit up to 10 days of fever and had a positivity rate of 93%. Peak period of detection ranged from 3 rd to 6 th day, (CI = 88, 98) and highest on the 4 th day of fever (28%) [Figure 2], which was found to be significant (P = 0.005, Fisher's Exact Test). This suggests that NS1 can be used as an early diagnostic marker for detection of dengue infection. This is supported by studies, where NS1 antigen has been detected from day 1 up to day 9 after the onset of fever in 82-83% of patients with dengue infection. [16],[17],[18],[19] In contrast, IgM antibodies were not detectable prior to day 3 of the illness. IgM was detectable by the 4 th day of fever with a positivity rate of 11% (CI = 5, 7). [Figure 2] shows the correlation of duration of fever and detection of NS1/IgM/IgG.
Figure 2: Correlation of duration of fever and detection of NS1/IgM/IgG


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Rapid intervention is required to avoid associated risk of thrombocytopenia and rapid downhill course of the disease. IgM alone and NS1 with IgM detection were associated with thrombocytopenia in 67% and 78% respectively, whereas 49% of cases who were positive only to NS1 antigen, had thrombocytopenia. [Figure 3] shows the comparison of various dengue specific parameters with platelet count.
Figure 3: Comparison of various dengue specific parameters with platelet count


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In pediatric age group, the platelet count normally ranges from 1.5 lakhs to 4.5 lakhs. During DF, the platelet count can decrease below 10,000/cu mm leading to DHF and DSS. [20] One of the risk factors for DHF is subsequent infection and presence of IgG. However, in our series of cases, DHF was not associated with the presence of IgG. In the present study, thrombocytopenia was noted in 50% of the cases. Among these cases, 24 of the children required platelet transfusion and 21 of them were positive for NS1. This indicates that NS1 can be a marker for decreasing platelet count. One of the children had platelet count as low as 12,000. All these children recovered with supportive treatment of antipyretics and fluid replacement. Hence, regular monitoring of platelet count is necessary to avoid risk in children.

To conclude, combination of clinical findings with rapid NS1 and IgM detection helped in confirming the diagnosis of dengue in children and initiating appropriate management. NS1 antigen is a promising early diagnostic marker. Accurate diagnosis of dengue infection requires a combination of several tests performed through an algorithm at different stages of the disease. Detailed serological and virological studies are required even during an outbreak for effective management to decrease morbidity and mortality among children.

 
   References Top

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Hastead SB. Dengue fever and dengue hemorrhagic fever. Nelson Textbook of Pediatrics. 18 th ed. Philadelphia: WB Saunders; 2007.  Back to cited text no. 1
    
2.
Centers for Disease Control and Prevention (CDC). Dengue hemorrhagic fever - U.S.-Mexico border, 2005. MMWR Morb Mortal Wkly Rep 2007;56:785-9.  Back to cited text no. 2
    
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WHO. Dengue Hemorrhagic Fever: Diagnosis, Treatment, Prevention and Control. 2 nd edition. 2 nd ed. Geneva: World Health Organization; 1997.  Back to cited text no. 3
    
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Gurdeep S. Dhooria, Deepak Bhat, Harmesh S. Bains. Clinical profile and outcome in children of dengue hemorrhagic fever in North India. Iran J Pediatr 2008;18:222-8.  Back to cited text no. 4
    
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Lee MS, Hwang KP, Chen TC, Lu PL, Chen TP. Clinical characteristics of dengue and dengue hemorrhagic fever in a medical center of southern Taiwan during the 2002 epidemic. J Microbiol Immunol Infect 2006;39:121-9.  Back to cited text no. 5
    
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World Health Organization. Scientific Working Group on Dengue. Geneva, Switzerland: World Health Organization; 2000.  Back to cited text no. 6
    
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Aggarwal A, Chandra J, Aneja S, Patwari AK, Dutta AK. An epidemic of dengue hemorrhagic fever and dengue shock syndrome in children in Delhi. Indian Pediatr 1998;35:727-32.  Back to cited text no. 9
    
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Kabra SK, Jain Y, Pandey RM, Madhulika, Singhal T, Tripathi P, et al. Dengue haemorrhagic fever in children in the 1996 Delhi epidemic. Trans R Soc Trop Med Hyg 1999;93:294-8.  Back to cited text no. 10
    
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Anderson KB, Chunsuttiwat S, Nisalak A, Mammen MP, Libraty DH, Rothman AL, et al. Burden of symptomatic dengue infection in children at primary school in Thailand: A prospective study. Lancet 2007;369:1452-9.  Back to cited text no. 12
    
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Shrivastava A, Dash PK, Tripathi NK, Sahni AK, Gopalan N, Lakshmana Rao PV. Evaluation of a commercial Dengue NS1 enzyme-linked immunosorbent assay for early diagnosis of dengue infection. Indian J Med Microbiol 2011;29:51-5.  Back to cited text no. 16
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Correspondence Address:
Dr. Shashikala Nair
Department of Clinical Microbiology, Pondicherry Institute of Medical Sciences, Kalapet, Puducherry - 605 014
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.162865

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