|
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*, Kings Institute of Preventive
Medicine, Chennai.
Correspondence to: Dr.
Manjith Narayanan, 4, Rohini Street, Rajaji Nagar, Villivakkam,
Chennai 600 049, India.
E-mail: doctormn76@hotmail.com
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 Kings 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 fishers 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.
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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.
|
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