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Brief Reports

Indian Pediatrics 2002; 39:1027-1033

Dengue Fever Epidemic in Chennai - A Study of Clinical Profile and Outcome


Manjith Narayanan, M.A. Aravind, N. Thilothammal, R. Prema, C.S. Rex Sargunam and Nalini Ramamurty*

From the Institute of Social Pediatrics, Government Stanley Medical College and Hospital, Chennai, and Department of Virology*, King’s Institute of Preventive Medicine, Chennai.

Correspondence to: Dr. Manjith Narayanan, 4, Rohini Street, Rajaji Nagar, Villivakkam, Chennai 600 049, India.

E-mail: [email protected]

Manuscript received: January 29, 2002; Initial review completed: February 26, 2002;

Revision accepted: May 13, 2002.

 

Children with dengue fever presenting to the Institute of Social Pediatrics, Government Stanley Hospital, during the months of October to December 2001, were prospectively followed up for clinical profile and outcome. Commonest clinical features were fever, vomiting, bleeding, body pain and hepatomegaly. Elevated liver enzymes and low platelet counts were common laboratory findings in dengue. Hepatomegaly, positive tourniquet test, elevated haematocrit and thrombocytopenia were more common in DHF and DSS group. Retro-orbital pain was slightly more in DHF and DSS groups and there was a tendency for DSS to present at an earlier age. There was no correlation between platelet counts and bleeding in classical dengue cases.

Key words: Dengue, Epidemic.


Dengue is the most important of the arboviral infections of humans(1). Global incidence of Dengue fever (DF) and Dengue hemorrhagic fever(DHF) has increased dramatically in the recent decades(1,2). In India, epidemics are becoming more frequent(1,2). Involvement of younger age group and increase in the frequency of epidemics are indicators of higher incidence of infection(1). If untreated, mortality from complications of DF is as high as 20%, whereas if recognized early and managed properly, mortality is less than 1%(2). Early diagnosis is essential and clinical suspicion is based on the frequency of symptoms in the population. Additional data about the disease lead to implementation or alteration of public health programs. Thus there is a need to keep track of various manifestations and gather descriptive data of the disease in each epidemic.

Subjects and Methods

This propective study was done on cases of DF/DHF reporting at Institute of Social Pediatrics, Government Stanley Medical College, Chennai between 9th October 2001 and 31st December 2001 when dengue epidemic occurred in Chennai. A total of 89 children identified as probable cases by clinical suspicion (any acute febrile illness with one of the following: myalgia, headache, retro-orbital pain, bleeding, altered sensorium, shock or low platelet count) were registered in the study, informed consent was obtained and detailed clinical history was taken. For all cases, the rapid IgM-IgG capture ELISA test, which has become the standard for serological diagnosis of dengue fever(3), was done at King’s Institute of Preventive Medicine, Guindy, Chennai. Children positive for IgM alone or both IgM and IgG were followed up for clinical profile. Cases of typhoid and leptospirosis were excluded by serological tests done at the appropriate time interval after the onset of fever. Cases where malarial parasite was seen in peripheral smear were also excluded. The number of cases included based on the above criteria was 59, including two children who satisfied WHO criteria(1) for the diagnosis of DHF but expired before serodiagnosis. Children who were dengue seropostive were classified on basis of WHO criteria(1) as follows: (i) dengue fever (DF): dengue seropositive without bleed; (ii) dengue fever with unusual bleed (DFB): dengue seropositive with bleeding tendencies, not satisfying WHO criteria(1) for DHF; (iii) dengue hemorrhagic fever (DHF); and (iv) dengue shock syndrome (DSS): evidence of peripheral circulatory failure.

Laboratory investigations carried out in these patients included hemoglobin, total and differential leukocyte count, hematocrit, platelet count, liver function tests and urine examination. Complete blood counts including hematocrit were repeated daily during the acute phase of the illness. Chest x-ray was taken to demonstrate pleural effusion in all cases. CSF analysis was done in patients with convulsions or meningeal signs.

The clinical manifestations and laboratory findings of each group of illness were compared using chi-square or fisher’s exact test for proportions and analysis of variance (ANOVA) for continuous data. The statistical package used was PEPI version 4.0 for windows (Abramson JH and Gahlinger PM (2001), Sagebrush press, Salt Lake City). Cases were managed according to the WHO protocol(1) and outcome was analyzed.

Results

Fifty nine seropostive cases were reported in our hospital during the study period of which 5 were DSS, 11 were DHF, 23 were DFB and 20 were DF. The age group of the affected children was between 7 months to 12 years (mean 6.76, SD 3.19) (Table I), with a modal age group of 5-6 years(14 children). DSS occurred at a lower age group than other complications of dengue fever, but the difference was not statistically significant (P = 0.27). Manifestations of dengue fever were equally common between the sexes.

Table I- Symptoms and Signs of Dengue Cases
S.No.
Feature
Dengue
infection
DF
DFB
DHF
DSS
P Value
1
Number of cases
59
20
23
11
5
2
Mean age, y(s.d.)
6.8 (3.2)
7.1(3)
6.4(3.3)
7.8(3.5)
4.6(1.8)
0.27
3
Male sex,no.(%)
31(52.4)
10(50)
12(52.2)
7(63.6)
2(40)
0.9
Symptoms
4
Fever, no.(%)
58(98.3)
20(100)
22(95.7)
11(100)
5(100)
5
Mean duration of fever
days:(s.d.)
4.9(2.3)
5.5(2.7)
4.9(1.9)
4.6(2.3)
3.2(1.0)
0.26
6
Vomiting, no.(%)
49(83)
16(80)
18(78.2)
10(90.1)
5(100)
0.4
7
Bleeding, no.(%)
39(66.1)
0(0)
23(100)
11(100)
5(100)
8
Body pain, no.(%)
32(54.2)
12(60)
12(52.2)
6(54.5)
2(40)
0.8
9
Headache, no.(%)
17(28.8)
6(30)
7(30.4)
3(27.2)
1(20)
0.9
10
Drowsiness, no.(%)
14(23.7)
5(25)
6(26.1)
1(9.1)
2(40)
0.8
11
Abdominal pain, no.(%)
14(23.7)
4(20)
6(26.1)
4(36.4)
0(0)
0.5
12
Bleeding from >1 site,no(%)
10(17)
0(0)
5(21.7)
3(27.3)
2(40)
0.5
13
Retro-orbital pain, no.(%)
7(11.9)
0(0)
3(13)
3(27.3)
1(20)
0.074
Signs
14
Hepatomegaly, no.(%)
31(52.5)
12(60)
7(30.4)
8(72.7)
4(80)
0.025
15
Tourniquet+ve, no.(%)
14(23.7)
0(0)
5(21.7)
4(36.3)
5(100)
0.027
16
Shock, no. (%)
13(22.0)
5(25)
3(13.0)
0(0)
5(100)
0.37
17
Conj. suffusion, no.(%)
9(15.3)
3(15)
4(17.4)
2(9.1)
0(0)
1
18
3rd space fluid, no(%)
6(10.2)
1(5)
1(4.3)
3(27.2)
1(20)
0.12
19
Lymphadenopathy, no.(%)
6(10.2)
1(5)
4(17.4)
1(9.1)
0(0)
0.68
20
Bradycardia, no. (%)
6(10.2)
2(10)
1(4.4)
2(18.1)
1(20)
0.3
21
Rashes, no.(%)
5(8.5)
1(5)
3(13)
1(9.1)
0(0)
0.9

 

Most common presentations were fever (98.3%), vomiting (83.0%), bleeding manifestations (66%) and myalgia (54.2%) (Table I). Fever, vomiting and body pain was the commonest combination of symptoms on presentation (19 patients). Fever was high grade, intermittent, and associated with rigors in 93%, 72.4% and 58.6% cases respectively. The mean duration of fever at the time of admission to the hospital was 4.89 days (SD = 2.3). The average duration of fever was lesser in the DSS group though the difference was not statistically significant (P = 0.26).

Table II- Investigations and Management of Dengue Seropositive Cases
S.
No.
Investigation
Dengue
infection
DF
DFB
DHF
DSS
P Value
1
Mean Hemoglobin, g/dL(s.d.)
10.8(1.1)
10.8(0.6)
11.1(0.7)
10.3(1.9)
11.4(1.5)
0.35
2.
Hematocrit, mean (s.d.)
33.2(3.3)
32.2(2.0)
32.1(2.4)
35.2(5.6)
37.6(2.9)
0.0002
3.
Fall of hematocrit
>20% on therapy, no.(%)
14(24.1)
1(5)
0(0)
9(81.8)
4(80)
 
4.
Platelet count cells/
cumm, mean
89559
96550
108782
60909
36200
0.008
5.
Platelet count
>100000/cumm,no(%)
16
5
11
0
0
0.35+
6.
Platelet count 50001-
100000/cumm, no(%)
31
13
11
6
1
0.0041**
7.
Platelet count £ 50000/
cumm, no(%)
12
2
1
5
4
 
8.
Differential lymphocyte
count > 50%, no(%)
18(31.6)
8(40)
6(26.1)
3(27)
1(33)*
0.52
9.
AST > 50 IU/L, no(%)
42(71.9)
16(80)
14(60.9)
9(81.8)
2(66)*
0.39
10.
ALT > 50 IU/L, no.(%)
34(59.7)
13(65)
12(52.1)
7(63.6)
2(66)*
0.69
11.
S. Alkaline Phosphatase
>200 IU/L, no(%)
24(42.1)
11(55)
5(21.7)
5(45.4)
2(66)*
0.07
12.
Urine albumin present
20(33.9)
8(40)
7(30.4)
4(36.3)
1(20)
0.8
* certain tests in DSS group were performed only in 3 children.
+P value for no difference in bleeding tendencies between DF and DFB group with respect to 
platelet count = 0.35
**P value for no difference in platelet counts between DF, DFB and (DHF+DSS) groups = 0.0041

 

Bleeding tendency was seen in 39 patients. Tourniquet test was positive in 14 (23.7%) and this was the only bleeding tendency noted in 5 cases. Patients with DHF and DSS had a higher proportion of tourniquet test positivity ( P = 0.02). Frank bleeding was noted in 34 cases and hematemesis was the commonest bleeding tendency (61.7%). The other sites of bleeding were skin (32.3%), nose (20.7%), gums (11.7%) and lungs (3%). Ten children had bleeding from multiple sites.

On clincal examination the most consistent finding was hepatomegaly. DF and DFB cases had significantly lesser hepatomegaly. Other findings included epigastric tenderness in 13 (22%) and splenomegaly in 7 (11.8%) cases respectively, besides those shown in Table I. Meningeal signs were noted in three cases. Though there were 13 children with shock, only 5 were classified as DSS because rest of the cases did not show evidence of plasma leakage.

Laboratory investigations (Table II) revealed a large proportion of midly anemic patients among our cases. A hematocrit more than 40 was noted in only 2 children (one DSS and one DHF). Mean hematocrit was significantly higher in the DHF and DSS groups (P = 0.0002). A fall of hematocrit by more than 20% on treatment was noted in 14 cases, predominantly DSS or DHF. Platelet counts were also significantly lower in the DHF and DSS groups ( P = 0.0041). There was no correlation between the platelet counts and bleeding in classical dengue fever (DF vs DFB, P = 0.35).

Liver enzymes were markedly elevated in more than 60% of the children who were dengue seropositive. Aspartate aminotran-sferase(AST) was elevated in a larger proportion of the patients. There was no significant difference between the subgroups of dengue with respect to liver function tests. Albuminuria was seen in a third of the patients. CSF analysis was normal in all the three patients with meningeal signs.

Discussion

The age group affected by dengue fever and its complications is lower in this study compared to previous Indian studies. This supports the view that endemicity of dengue fever is increasing in India. Among the subgroups of dengue there is a distinct tendency for DSS to occur at lower age, though the difference is not statistically significant. However, previous studies have not noted any difference in age between dengue with and without shock(4-7).

Fever and vomiting were the most frequent symptoms and hepatomegaly was the most frequent sign in these children, as observed in earlier studies(5,7,8). Vomiting and retro-orbital pain are slightly more common in DSS and DHF group than the others, though the difference is not statistically significant. Hepatomegaly is a less frequent finding among adults as reported in Philippines and Delhi(9,10). We found hepatomegaly to be more in DHF and DSS groups than others, in contrast to previous studies(7,11).

Hematemesis is the most common bleeding manifestation in our cases as reported in other studies on Indian children(5,8,11). Studies in other countries especially South-East Asian countries, report tourniquet test positivity as the commonest bleeding manifestation(4,9). Low proportion of positive tourniquet test in Indian studies(5,6,8,10,11) may be due to the darker skin colour or may be the result of different strain of the dengue virus affecting the Indian subcontinent. The proportion of patients having positive tourniquet test among those with frank bleeding is 26.4%(9/34) which is not very different from the proportion among those without frank bleeding 20% (5/25). Thus tourniquest test does not correlate well with other bleeding manifestations in dengue fever, similar to the finding reported by Wali et al(12). This may be because tourniquet test positivity and other bleeding manifestations have different pathogenesis. This has resulted in the modified 1997 WHO criteria for DHF(1), where tourniquet test is no longer essential for the diagnosis of DHF.

There is a low proportion of children with evidence for hemoconcentration in our study group. If this was not taken as an essential criteria for DHF as in Aggarwal et al.(8), nine more cases could have been included in DHF group and three more in DSS group. The overall mean hematocrit value in the non DHF/DSS group was only 32.2%. Thus it is necessary to conduct studies towards defining the cutoff points for raised hematocrit to diagnose DHF in Chennai population as conducted by Gomber et al(6) in Delhi, which identified the cutoff value as 36.3%. In cases without evidence for hemoconcentration (DF or DFB), there was no correlation between platelet count and bleeding manifestation. This supports the finding by other studies of the important contribution of factors other than thrombocytopenia in bleeding in dengue fever cases(7,10). However studies which include only DHF cases show correlation between platelet count and bleeding manifestations(12). This gives further evidence that bleeding manifestations due to classical dengue fever (DFB) are multifactorial.

The other important laboratory finding is the rise in serum levels of liver enzymes (LFTs) as reported in various studies(4,11,13). However, our study failed to demonstrate a significant difference in the LFTs between the subgroups of Dengue, unlike other studies(5,13). The high incidence of vomiting, hepatomegaly and elevated liver enzymes can serve as markers for suspicion of dengue during an epidemic. Subclinical hepatitis may contribute to the abdominal pain and vomiting in these children.

The mortality in our series was comparable with other Indian studies(5,8,10). Both the children who died had DSS and expired within 24 hrs of hospitalization . In these cases, the period of defervescence preceding shock was found to produce a sense of complacency in parents and contributed to the late presentation at the hospital. Hence health education regarding manifestations of DSS is important during an epidemic. It needs to be emphasized that a child between 1-6 years becoming drowsy or cold after a period of fever lasting 3-4 days has to be immediately brought to the hospital.

To conclude, this study shows that DF is becoming more prevalent in India. In children, importance should be given to symptoms like fever, vomiting, bleeding and musculoskeletal pain. If these are associated with hepatomegaly and elevated liver enzymes in context of a low platelet count, a strong possibility of DF or DHF is present, especially in an epidemic setting. There are few symptoms or signs which can reliably differentiate between DF, DFB, DHF and DSS. Retro-orbital pain, hepatomegaly and positive tourniquet test are certain markers that predict DHF.

Contributors: MN, MAA, NT, RP and CSR were involved in concept and design of the study, collection and analysis of data and drafting and analysis of the article. NR helped in designing the study and revised the manuscript. MN shall act as guarantor for the paper.

Funding: None.

Competing interests: None stated.

Key Messages

• In a child presenting with fever, vomiting and bleeding, associated with hepatomegaly, elevated liver enzymes and low platelet count, a diagnosis of dengue fever is a strong possibility especially in an epidemic setting.

• A rise of hematocrit does not help much in the diagnosis of dengue hemorrhagic fever in the Indian population due to the high prevalence of anemia.

• There are few symptoms or signs that reliably differentiate between DF, DFB, DHF and DSS.

 

 

 References


1. World Health Organization. Dengue Hemorrhagic Fever: Diagnosis, Treatment, Prevention and Control. 2nd edition. Geneva, World Health Organization, 1997.

2. World Health Organization. WHO report on global surveillance of Epidemic prone infectious diseases. http://www/who.int/emc-documents/surveillance/docs/whocdscsrisr 2001.html

3. Vaughn DW, Nisalak A, Solomon T, Kalyanarooj S, Nguyen MD, Kneen R, et al. Rapid serologic diagnosis of dengue virus infection using a commercial capture ELISA that distinguishes primary and secondary infections. Am J Trop Med Hyg 1999; 60: 639-698.

4. Kalayanarooj S, Vaughn DW, Nimmannitya S, Green S, Suntayakorn S, Kunentrasai N, et al. Early clinical and laboratory indicators of acute dengue illness. J Infect Dis 1997; 176: 313-321.

5. Srivastava VK, Suri S, Bhasin A, Srivastava L, Bharadwaj M. An epidemic of dengue hemorrhagic fever and dengue shock syndrome in Delhi: a clinical study. Ann Trop Pediatr 1990; 10: 329-334.

6. Gomber S, Ramachandran VG, Kumar S, Agarwal KN, Gupta P, Gupta P, et al. Hematological observations as diagnostic markers in dengue hemorrhagic fever - a reappraisal. Indian Pediatr 2001; 38: 477-481.

7. Bethell DB, Gamble J, Loc PP, Dung NM, Chau TTH, Loan HT, et al. Non-invasive measurement of microvascular leakage in patients with dengue hemorrhagic fever. Clin Infect Dis 2001; 32: 243-253.

8. 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: 727-732.

9. Hayes CG, Manaloto CR, Gonzales A, Ronoa CP. Dengue infections in the Philippines: clinical and virological findings in 517 hospitalized patients. Am J Trop Med Hyg 1988; 39: 110-116

10. Tripathi BK, Gupta B, Sinha RS, Prasad S, Sharma DK. Exprience in adult population in dengue outbreak in Delhi. J Assoc Physicians India 1998; 46: 273-276.

11. Pushpa V, Venkatadesikalu M, Mohan S, Cherian T, John TJ, Ponnuraj EM. An epidemic of dengue haemorrhagic fever/dengue shock syndrome in tropical India. Ann Trop Pediatr 1998; 18: 289-293.

12. Wali JP, Biswas A, Aggarwal P, Wig N, Handa R. Validity of tourniquet test in dengue hemorrhagic fever. J Assoc Physicians India. 1999; 47: 203-204.

13. Kuo CH, Tai DI, Chang-Chien CS, Lan CK, Chiou SS, Liaw YF. Liver biochemical tests and dengue fever. Am J Trop Med Hyg. 1992; 47: 265-270.

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