J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 4, Number 1, February 2012, pages 33-44

Simple Prognostic Criteria can Definitively Identify Patients who Develop Severe Versus Non-Severe Dengue Disease, or Have Other Febrile Illnesses

**Table 1.** Viral and/or Serological Confirmation of DENV Infections in 33/100 Patients
No	Age (y)	DOC^a	Virus^b	1/log₁₀ ELISA titer (OD at 1/100 dilution)^c	Clinical^d Classification
^aDOC: day of S1 and S2 serum collection after the onset of fever. ^bDengue (-1 to -4) virus serotype isolated. ^cReciprocal log10 50% end-point IgM and IgG ELISA titers and optical densities (ODs) at 1/100 dilutions (in brackets) to identify primary (P) or secondary (S) DENV infections using ≥ 2.6 and < 2.6 and ≥ 1.8 and < 1.8 IgM:IgG OD ratios on their S1 and S2 samples, respectively, or high S1 IgG primary (P), high S1 IgM secondary (S) or low S2 IgG secondary (*LS) infections [8]. ^dClinical classifications as non-severe dengue disease (N-SDD) or severe dengue disease (SDD) with the DHF (I to IV) grade in brackets.
1	19	0	6	-	-(0.4)	-(0.7)	0.6(S)	3.5(1.5)	5.6(1.6)	0.9(S)	N-SDD
2	14	1	9	D-2V	-(0.2)	-(0.5)	0.4(S)	4.1(1.6)	6.6(1.6)	1.0(S)	SDD(DHF I)
3	10	1	4	D-2V	-(0.5)	-(0.3)	1.7(S)	3.2(1.3)	5.6(1.6)	0.8(S)	N-SDD
4	6	1	5	D-2V	-(0.4)	-(0.2)	2.0(S)	3.3(1.5)	6.6(1.6)	0.9(S)	N-SDD
5	7	1	4	-	-(0.3)	-(0.7)	0.4(S)	2.3(1.0)	-(0.32)	3.1(*P)	N-SDD
6	6	1	3	D-2V	3.2(1.3)	-(0.3)	4.3(P)	3.2(1.4)	5.4(1.6)	0.9(*S)	N-SDD
7	11	1	10	D-2/-3V	-(0.6)	4.3(1.1)	0.6(S)	3.4(1.0)	6.3(1.6)	0.6(S)	N-SDD
8	1	1	10	-	-(0.7)	-(0.2)	3.5(P)	2.9(1.3)	-(0.3)	4.3(P)	N-SDD
9	8	2	4	D-2V	-(0.4)	4.2(1.2)	0.3(S)	2.9(1.0)	5.7(1.6)	0.6(S)	SDD(DHF III)
10	22	2	7	D-2V	-(0.2)	4.4(1.1)	0.2(S)	3.1(1.0)	6.7(1.6)	0.6(S)	SDD(DHF II)
11	7	2	8	D-2V	-(0.3)	-(0.1)	3(P)	3.7(1.5)	4.9(1.5)	1(*S)	N-SDD
12	9	2	6	-	2.1(0.9)	4.5(0.9)	1(S)	2.9(1.2)	6(1.6)	0.8(S)	N-SDD
13	2	2	6	-	-(0.5)	-(0.3)	1.7(S)	4.6(1.6)	3.5(1.4)	1.1(*LS)	N-SDD
14	18	2	8	D-2V	-(0.3)	5(1.2)	0.3(S)	3.9(1.3)	5.8(1.6)	0.8(S)	SDD(DHF II)
15	10	2	5	D-2V	-(0.3)	-(0.1)	3(P)	3.2(1.4)	4.9(1.5)	0.9(*S)	N-SDD
16	8	2	8	D-2V	-(0.4)	-(0.2)	2(S)	3.6(1.6)	5.7(1.6)	1(S)	N-SDD
17	10	2	5	-	-(0.8)	-(0.4)	2(S)	3.6(1.6)	6.6(1.6)	1(S)	N-SDD
18.0	6	2	9	D-2V	-(0.5)	-(0.3)	1.7(S)	3.5(1.6)	5.6(1.6)	1(S)	N-SDD
19	27	2	7	D-1V	-(0.4)	4.2(0.8)	0.5(S)	2.9(1.0)	5.7(1.6)	0.6(S)	N-SDD
20	11	2	8	-	-(0.6)	4.6(1.0)	0.6(S)	3.2(1.3)	6.1(1.6)	0.8(S)	N-SDD
21	6	2	4	D-2V	-(0.3)	-(0.1)	3(P)	2.6(1.1)	-(0.4)	2.8(P)	N-SDD
22	14	2	5	D-3V	-(0.3)	-(0.2)	1.5(S)	-(0.8)	5.2(1.6)	0.5(S)	N-SDD
23	9	2	8	D-2V	-(0.3)	4.7(1.1)	0.3(S)	-(0.6)	6.3(1.6)	0.4(S)	N-SDD
24	6	3	5	D-2V	-(0.6)	-(0.7)	0.9(S)	3.6(1.6)	5.3(1.6)	1(S)	N-SDD
25	11	3	9	D-2/-4V	-(0.3)	-(0.5)	0.6(S)	-(0.5)	5.9(1.5)	0.3(S)	N-SDD
26	11	3	9	-	-(0.4)	2.1(0.9)	0.4(S)	2.3(0.9)	6.1(1.6)	0.6(S)	N-SDD
27	11	3	13	-	-(0.4)	-(0.6)	0.7(S)	-(0.7)	6.8(1.6)	0.4(S)	N-SDD
28	7	3	6	D-2V	-(0.2)	-(0.6)	0.3(S)	3.0(1.1)	6.5(1.6)	0.7(S)	SDD(DHF III)
29	6	3	5	-	-(0.13)	4.5(1.4)	0.9(S)	3.5(1.3)	6.2(1.6)	0.8(S)	N-SDD
30	11	3	5	-	2.8(1.0)	-(0.6)	1.7(S)	3.7(1.3)	5.9(1.6)	0.8(S)	N-SDD
31	7	3	5	-	3.5(1.6)	5.3(1.6)	1(S)	3.9(1.6)	6.2(1.6)	1(S)	N-SDD
32	7	3	10	-	3.5(1.4)	5(1.6)	0.9(S)	4(1.6)	6(1.6)	1(S)	N-SDD
33	7	3	10	-	1.7(0.9)	4.6(1.2)	0.8(S)	3(1.5)	5.9(1.6)	0.9(S)	N-SDD

Table 1. Viral and/or Serological Confirmation of DENV Infections in 33/100 Patients

Age (y)

DOC^a

Virus^b

1/log₁₀ ELISA titer (OD at 1/100 dilution)^c

Clinical^d Classification

IgM/IgG OD ratio (P/S)

IgM

IgG

IgM

IgG

^aDOC: day of S1 and S2 serum collection after the onset of fever. ^bDengue (-1 to -4) virus serotype isolated. ^cReciprocal log10 50% end-point IgM and IgG ELISA titers and optical densities (ODs) at 1/100 dilutions (in brackets) to identify primary (P) or secondary (S) DENV infections using ≥ 2.6 and < 2.6 and ≥ 1.8 and < 1.8 IgM:IgG OD ratios on their S1 and S2 samples, respectively, or high S1 IgG primary (*P), high S1 IgM secondary (*S) or low S2 IgG secondary (*LS) infections [8]. ^dClinical classifications as non-severe dengue disease (N-SDD) or severe dengue disease (SDD) with the DHF (I to IV) grade in brackets.

-(0.4)

-(0.7)

0.6(S)

3.5(1.5)

5.6(1.6)

0.9(S)

N-SDD

D-2V

-(0.2)

-(0.5)

0.4(S)

4.1(1.6)

6.6(1.6)

1.0(S)

SDD(DHF I)

D-2V

-(0.5)

-(0.3)

1.7(S)

3.2(1.3)

5.6(1.6)

0.8(S)

N-SDD

D-2V

-(0.4)

-(0.2)

2.0(S)

3.3(1.5)

6.6(1.6)

0.9(S)

N-SDD

-(0.3)

-(0.7)

0.4(S)

2.3(1.0)

-(0.32)

3.1(*P)

N-SDD

D-2V

3.2(1.3)

-(0.3)

4.3(P)

3.2(1.4)

5.4(1.6)

0.9(*S)

N-SDD

D-2/-3V

-(0.6)

4.3(1.1)

0.6(S)

3.4(1.0)

6.3(1.6)

0.6(S)

N-SDD

-(0.7)

-(0.2)

3.5(P)

2.9(1.3)

-(0.3)

4.3(P)

N-SDD

D-2V

-(0.4)

4.2(1.2)

0.3(S)

2.9(1.0)

5.7(1.6)

0.6(S)

SDD(DHF III)

D-2V

-(0.2)

4.4(1.1)

0.2(S)

3.1(1.0)

6.7(1.6)

0.6(S)

SDD(DHF II)

D-2V

-(0.3)

-(0.1)

3(P)

3.7(1.5)

4.9(1.5)

1(*S)

N-SDD

2.1(0.9)

4.5(0.9)

1(S)

2.9(1.2)

6(1.6)

0.8(S)

N-SDD

-(0.5)

-(0.3)

1.7(S)

4.6(1.6)

3.5(1.4)

1.1(*LS)

N-SDD

D-2V

-(0.3)

5(1.2)

0.3(S)

3.9(1.3)

5.8(1.6)

0.8(S)

SDD(DHF II)

D-2V

-(0.3)

-(0.1)

3(P)

3.2(1.4)

4.9(1.5)

0.9(*S)

N-SDD

D-2V

-(0.4)

-(0.2)

2(S)

3.6(1.6)

5.7(1.6)

1(S)

N-SDD

-(0.8)

-(0.4)

2(S)

3.6(1.6)

6.6(1.6)

1(S)

N-SDD

18.0

D-2V

-(0.5)

-(0.3)

1.7(S)

3.5(1.6)

5.6(1.6)

1(S)

N-SDD

D-1V

-(0.4)

4.2(0.8)

0.5(S)

2.9(1.0)

5.7(1.6)

0.6(S)

N-SDD

-(0.6)

4.6(1.0)

0.6(S)

3.2(1.3)

6.1(1.6)

0.8(S)

N-SDD

D-2V

-(0.3)

-(0.1)

3(P)

2.6(1.1)

-(0.4)

2.8(P)

N-SDD

D-3V

-(0.3)

-(0.2)

1.5(S)

-(0.8)

5.2(1.6)

0.5(S)

N-SDD

D-2V

-(0.3)

4.7(1.1)

0.3(S)

-(0.6)

6.3(1.6)

0.4(S)

N-SDD

D-2V

-(0.6)

-(0.7)

0.9(S)

3.6(1.6)

5.3(1.6)

1(S)

N-SDD

D-2/-4V

-(0.3)

-(0.5)

0.6(S)

-(0.5)

5.9(1.5)

0.3(S)

N-SDD

-(0.4)

2.1(0.9)

0.4(S)

2.3(0.9)

6.1(1.6)

0.6(S)

N-SDD

-(0.4)

-(0.6)

0.7(S)

-(0.7)

6.8(1.6)

0.4(S)

N-SDD

D-2V

-(0.2)

-(0.6)

0.3(S)

3.0(1.1)

6.5(1.6)

0.7(S)

SDD(DHF III)

-(0.13)

4.5(1.4)

0.9(S)

3.5(1.3)

6.2(1.6)

0.8(S)

N-SDD

2.8(1.0)

-(0.6)

1.7(S)

3.7(1.3)

5.9(1.6)

0.8(S)

N-SDD

3.5(1.6)

5.3(1.6)

1(S)

3.9(1.6)

6.2(1.6)

1(S)

N-SDD

3.5(1.4)

5(1.6)

0.9(S)

4(1.6)

6(1.6)

1(S)

N-SDD

1.7(0.9)

4.6(1.2)

0.8(S)

3(1.5)

5.9(1.6)

0.9(S)

N-SDD

**Table 2.** Early Acute Phase- (< 72 Hour-) Clinical and Hematological Criteria of Patients Who Subsequently Developed Severe Dengue Disease (SDD) or Non-Severe Dengue Disease (N-SDD), or Had Fever of Unknown Origin (FUO)
Clinical/ hematological criteria	SDD (n = 5)	N-SDD (n = 28 )	FUO (n = 67)	p-value
Clinical or hematological criteria percentages, numbers, standard deviations (sd: +) and ranges (in brackets), with comparative p-values or non-significant differences (ns). WHO values for DENV infections are: ^apositive tourniquet test: >20 petechia/ inch²; ^bleukopenia: < 5,000/μl; ^cleukocytosis: > 10,000/μl; ^dneutropenia: < 40%; ^eneutrophilia: > 70%, and ^fthrombocytopenia: < 100,000/μl [4, 6].
Mean age (years) sd (range)	13.8 ± 6.4 (7 - 22)	8.8 ± 4.7 (1 - 19)	18.3 ± 15.8 (0.5 - 59)	0.047	ns	< 0.001
Abdominal pain (%)	100.0	0.0	0.0	< 0.001	< 0.001	ns
Eye pain (%)	80.0	76.2	56.7	ns	ns	ns
Joint pain (arthralgia) (%)	100.0	76.2	73.1	ns	ns	ns
Hepatomegaly > 2cm (%)	40.0	0.0	0.0	0.02	0.0030	ns
Jaundice (%)	0.0	0.0	20.9	ns	ns	ns
Vomiting (persistent) (%)	80.0	47.6	55.2	ns	ns	ns
Conjunctival injection (%)	100.0	0.0	0.0	< 0.001	< 0.001	ns
Gum bleeding (%)	20.0	9.5	4.5	ns	ns	ns
Petechia (%)	100.0	38.1	24.6	0.02	0.0010	ns
Tourniquet test positive (%)a	100.0	28.6	20.8	ns	< 0.001	ns
Venipuncture bleeding (%)	100.0	0.0	0.0	< 0.001	< 0.001	ns
Mean leukocytes (x103/ µl) sd (range)	4.3 ± 1.0 (3.1 - 5.8)	5.0 ± 1.8 (1.7 - 8.0)	8.0 ± 5.4 (7.2 - 35.3)	-	-	-
Leukopenia (%)b	60.0	62.0	17.8	ns	ns	0.0010
Leukocytosis (%)c	0.0	0.0	28.6	ns	ns	ns
Mean lymphocytes (%) sd (range)	11.8 ± 6.3 (4.3 - 18.6)	33.0 ± 12.6 (12.1 - 58.3)	30.4 ± 17.9 (6.6 - 35.4)	-	-	-
Lymphocytosis (%)	0.0	14.0	9.5	ns	ns	ns
Lymphopenia (%)	100.0	66.7	51.4	ns	ns	ns
Mean monocytes (%) sd (range)	4.6 ± 2.8 (1.5 - 8.5)	9.8 ± 4.6 (0.9 - 22.8)	8.3 ± 4.7 (0.5 - 28.6)	-	-	-
Monocytosis (%)	40.0	81.0	59.2	ns	ns	ns
Monocytopenia (%)	0.0	4.8	5.6	ns	ns	ns
Mean neutrophils (%) sd (range)	83.1 ± 7.8 (76.6 - 89.9)	57.4 ± 15.7 (27.9 - 85.5)	57.7 ± 20.7 (21.1 - 95.5)	-	-	-
Neutropenia (%)d	0.0	28.6	9.3	ns	ns	ns
Neutrophilia (%)e	100.0	23.8	50.7	0.0030	ns	ns
Mean platelets (x103/ µl) sd (range)	136.6 ± 43.1 (73.0 - 202.0)	226.4 ± 157.8 (134.0 - 393.0)	253.2 ± 114.0 (128.0 - 527.0)	-	-	-
Thrombocytopenia (%)f	20.0	0.0	0.0	ns	ns	ns
Mean hematocrit (%) sd (range)	35.6 + 5.2 (28.0 - 41.3)	36.0 ± 3.3 (27.8 - 40.9)	36.1 ± 4.8 (33.7 - 38.6)	-	-	-
Haematocrit > 20% (%)	0.0	0.0	0.0	ns	ns	ns

Table 2. Early Acute Phase- (< 72 Hour-) Clinical and Hematological Criteria of Patients Who Subsequently Developed Severe Dengue Disease (SDD) or Non-Severe Dengue Disease (N-SDD), or Had Fever of Unknown Origin (FUO)

Clinical/ hematological criteria

SDD (n = 5)

N-SDD (n = 28 )

FUO (n = 67)

p-value

SDD vs N-SDD

SDD vs FUO

N-SDD vs FUO

Clinical or hematological criteria percentages, numbers, standard deviations (sd: +) and ranges (in brackets), with comparative p-values or non-significant differences (ns). WHO values for DENV infections are: ^apositive tourniquet test: >20 petechia/ inch²; ^bleukopenia: < 5,000/μl; ^cleukocytosis: > 10,000/μl; ^dneutropenia: < 40%; ^eneutrophilia: > 70%, and ^fthrombocytopenia: < 100,000/μl [4, 6].

Mean age (years) sd (range)

13.8 ± 6.4 (7 - 22)

8.8 ± 4.7 (1 - 19)

18.3 ± 15.8 (0.5 - 59)

0.047

< 0.001

Abdominal pain (%)

100.0

0.0

< 0.001

Eye pain (%)

80.0

76.2

56.7

Joint pain (arthralgia) (%)

100.0

76.2

73.1

Hepatomegaly > 2cm (%)

40.0

0.0

0.02

0.0030

Jaundice (%)

0.0

20.9

Vomiting (persistent) (%)

80.0

47.6

55.2

Conjunctival injection (%)

100.0

0.0

< 0.001

Gum bleeding (%)

20.0

9.5

4.5

Petechia (%)

100.0

38.1

24.6

0.02

0.0010

Tourniquet test positive (%)a

100.0

28.6

20.8

< 0.001

Venipuncture bleeding (%)

100.0

0.0

< 0.001

Mean leukocytes (x103/ µl) sd (range)

4.3 ± 1.0 (3.1 - 5.8)

5.0 ± 1.8 (1.7 - 8.0)

8.0 ± 5.4 (7.2 - 35.3)

Leukopenia (%)b

60.0

62.0

17.8

0.0010

Leukocytosis (%)c

0.0

28.6

Mean lymphocytes (%) sd (range)

11.8 ± 6.3 (4.3 - 18.6)

33.0 ± 12.6 (12.1 - 58.3)

30.4 ± 17.9 (6.6 - 35.4)

Lymphocytosis (%)

0.0

14.0

9.5

Lymphopenia (%)

100.0

66.7

51.4

Mean monocytes (%) sd (range)

4.6 ± 2.8 (1.5 - 8.5)

9.8 ± 4.6 (0.9 - 22.8)

8.3 ± 4.7 (0.5 - 28.6)

Monocytosis (%)

40.0

81.0

59.2

Monocytopenia (%)

0.0

4.8

5.6

Mean neutrophils (%) sd (range)

83.1 ± 7.8 (76.6 - 89.9)

57.4 ± 15.7 (27.9 - 85.5)

57.7 ± 20.7 (21.1 - 95.5)

Neutropenia (%)d

0.0

28.6

9.3

Neutrophilia (%)e

100.0

23.8

50.7

0.0030

Mean platelets (x103/ µl) sd (range)

136.6 ± 43.1 (73.0 - 202.0)

226.4 ± 157.8 (134.0 - 393.0)

253.2 ± 114.0 (128.0 - 527.0)

Thrombocytopenia (%)f

20.0

0.0

Mean hematocrit (%) sd (range)

35.6 + 5.2 (28.0 - 41.3)

36.0 ± 3.3 (27.8 - 40.9)

36.1 ± 4.8 (33.7 - 38.6)

Haematocrit > 20% (%)

0.0