approximately 50100 million infected cases were reported annually . among those infected , 500000 patients had severe infection and required hospital admission ; most were children .
the cost of care was as high as $ us 2.1 billion per year in the united states of america .
no specific treatments are available except for symptomatic , which are effective in early detection . in patients with severe infection ,
early detection or correct prognostication may avoid such severe complications [ 4 , 6 ] .
clinical risks and various laboratory results were studied to explore their roles in the prediction of dengue severity . among many of them were girls , children above 5 years of age , persistent abdominal pain , lethargy , cold hand and feet , hepatomegaly , abnormal bleeding , overweight , malnourished children , ascites , plural effusion , leucopenia ( white blood count < 4,000/l ) , thrombocytopenia , hemoconcentration , prolonged prothrombin time ( pt ) , prolonged partial thromboplastin time ( ptt ) , elevated aspartate aminotransferase ( ast ) , and alanine aminotransferase ( alt ) enzymes .
the scoring system , such as the pediatric logistic organ dysfunction ( pelod ) score and the disseminated intravascular coagulation ( dic ) score , was used to forecast mortality in dss .
a decision tree algorithm was used to differentiate dengue fever from other types of fever and also to forecast severity in dengue infection .
some studies applied dic scoring system to diagnose dic more precisely , using clinical signs and symptoms and routine laboratory investigations to differentiate dhf from df .
most of the prediction systems in the past focused on clinical outcomes of the disease .
the aim of the present study was to develop a simple clinical risk scoring system to predict dengue infection severity , based on patient clinical characteristics and routine laboratory investigations , obtained from the previous investigation .
the medical records of children aged 115 years with dengue infection between 2007 to 2010 in the three university - affiliated general hospitals located in the northern region of thailand , sawanpracharak hospital in nakorn sawan , uttaradit hospital in uttaradit , and kamphaeng phet hospital in kamphaeng phet , were reviewed .
the data were retrieved from the hospital database , under the following icd-10 : a90-dengue fever , a91-dengue hemorrhagic fever , and a910-dengue hemorrhagic fever with shock .
the patient characteristics with potential prediction includeddemographic : gender and age;mode of presentation : hepatomegaly , headache , myalgia , vomiting , cough , abdominal pain , rash , pleural effusion , petechiae , and any bleeding episodes;hemodynamic profiles : pulse pressure , systolic blood pressure ( sbp ) , and diastolic blood pressure ( dbp);hematological profiles : hematocrit , hemoglobin , white cell count , lymphocytes , neutrophils , and platelet;biochemical profiles : aspartate aminotransferase ( ast ) , alanine aminotransferase ( alt ) , prothrombin time ( pt ) , and partial thromboplastin time ( ptt ) .
demographic : gender and age ; mode of presentation : hepatomegaly , headache , myalgia , vomiting , cough , abdominal pain , rash , pleural effusion , petechiae , and any bleeding episodes ; hemodynamic profiles : pulse pressure , systolic blood pressure ( sbp ) , and diastolic blood pressure ( dbp ) ; hematological profiles : hematocrit , hemoglobin , white cell count , lymphocytes , neutrophils , and platelet ; biochemical profiles : aspartate aminotransferase ( ast ) , alanine aminotransferase ( alt ) , prothrombin time ( pt ) , and partial thromboplastin time ( ptt ) .
the severity of dengue infection was operationally defined by the following criteria : dengue infection ( df ) : acute or abrupt onset of fever , accompanied by a positive tourniquet test , and white blood count  5,000/l ; dengue hemorrhagic fever ( dhf ) : all of the following items : acute or abrupt fever for 27 days , at least one of the following bleeding episodes : positive tourniquet test , petechiae , ecchymoses , or purpura , bleeding from mucosa , gastrointestinal tract , injection sites , or other location , hematemesis or melena , platelet  100,000/l , at least one of the following plasma leakage evidence items : hemoconcentration assessed by an increase in hematocrit 20% from previous hematocrit , signs of plasma leakage , such as pleural effusion or ascites , or evidence of hypoalbuminemia;dengue shock syndrome ( dss ) : all items for dengue hemorrhagic fever above , accompanied with evidence of circulatory failure :  ( i ) rapid and weak pulse ,  ( ii ) pulse pressure  20  mmhg , or manifested by  ( i ) hypotension ,  ( ii ) cold body temperature or irritable . dengue infection
( df ) : acute or abrupt onset of fever , accompanied by a positive tourniquet test , and white blood count  5,000/l ; dengue hemorrhagic fever ( dhf ) : all of the following items : acute or abrupt fever for 27 days , at least one of the following bleeding episodes : positive tourniquet test , petechiae , ecchymoses , or purpura , bleeding from mucosa , gastrointestinal tract , injection sites , or other location , hematemesis or melena , platelet  100,000/l , at least one of the following plasma leakage evidence items : hemoconcentration assessed by an increase in hematocrit 20% from previous hematocrit , signs of plasma leakage , such as pleural effusion or ascites , or evidence of hypoalbuminemia ; acute or abrupt fever for 27 days , at least one of the following bleeding episodes : positive tourniquet test , petechiae , ecchymoses , or purpura , bleeding from mucosa , gastrointestinal tract , injection sites , or other location , hematemesis or melena , positive tourniquet test , petechiae , ecchymoses , or purpura , bleeding from mucosa , gastrointestinal tract , injection sites , or other location , hematemesis or melena , platelet  100,000/l , at least one of the following plasma leakage evidence items : hemoconcentration assessed by an increase in hematocrit 20% from previous hematocrit , signs of plasma leakage , such as pleural effusion or ascites , or evidence of hypoalbuminemia ; hemoconcentration assessed by an increase in hematocrit 20% from previous hematocrit , signs of plasma leakage , such as pleural effusion or ascites , or evidence of hypoalbuminemia ; dengue shock syndrome ( dss ) : all items for dengue hemorrhagic fever above , accompanied with evidence of circulatory failure :  ( i ) rapid and weak pulse ,  ( ii ) pulse pressure  20  mmhg , ( i ) rapid and weak pulse , ( ii ) pulse pressure  20  mmhg ,  ( i ) hypotension ,  ( ii ) cold body temperature or irritable .
dengue severity was classified into 4 grades , based on bleeding episodes and shock , as follows :  grade 1 : no evidence of bleeding , positive tourniquet test ,  grade 2 : evidences of bleeding episodes ,  grade 3 : presence of week and rapid pulse rate , low blood pressure , or narrow pulse pressure ,  grade 4 : nonmeasurable blood pressure or nonpalpable pulse . 
grades 1 - 2 were classified as dhf and grades 3 - 4 were classified as dss .
grade 1 : no evidence of bleeding , positive tourniquet test , grade 2 : evidences of bleeding episodes , grade 3 : presence of week and rapid pulse rate , low blood pressure , or narrow pulse pressure , grade 4 : nonmeasurable blood pressure or nonpalpable pulse .
grades 1 - 2 were classified as dhf and grades 3 - 4 were classified as dss .
potential predictors for dengue severity from a previous report   were tested with nonparametric test for trend .
the predictive ability was analyzed by multivariable ordinal logistic regression and presented with coefficients and odds ratios .
the total ( sum ) scores were used to classify patients into 3 severity levels .
the present investigation was approved by the research ethical committee of the faculty of medicine , chiang mai university , and the research ethical committees of the three hospitals .
a total of 777 patients with dengue infection were classified based on the above criteria into 3 severity levels : df ( n = 391 ) , dhf ( n = 296 ) , and dss ( n = 90 ) . under the univariable analysis ,
the three severity groups were similar in gender ( p = 0.888 ) , age ( p = 0.903 ) , presence of vomiting ( p = 0.187 ) , cough ( p = 0.425 ) , rash ( p = 0.124 ) , and dbp ( p = 0.084 ) but were difference according to the presence of hepatomegaly , headache , myalgia , abdominal pain , pleural effusion , petechiae , bleeding episodes , sbp , pulse pressure , hematocrit , hemoglobin , white cell count , lymphocytes , neutrophils , platelets , ast , alt , pt , and ptt ( table 1 ) . under the multivariable analysis ,
the clinical characteristics with significant predictive ability for dengue severity included age > 6 years ( or = 1.46 , 95% ci = 1.121.91 , p = 0.005 ) , hepatomegaly ( or = 12.31 , 95% ci = 8.8417.15 , p < 0.001 ) , hematocrit  40% ( or = 1.34 , 95% ci = 1.101.64 , p = 0.003 ) , sbp < 90  mmhg ( or = 1.70 , 95% ci = 1.322.17 , p < 0.001 ) , white cell count > 5000/l ( or = 1.40 , 95% ci = 1.131.75 , p = 0.002 ) , and platelet  50000/l ( or = 3.95 , 95% ci = 3.144.96 , p < 0.001 ) .
the strongest predictors were hepatomegaly ( or = 12.31 ) and platelet  50000/l ( or = 3.95 ) ( table 2 ) .
transformation of significant parameter coefficients into item scores was done by division of each coefficient with the smallest coefficient of the model ( 0.30 ) and rounded up or down to the nearest 0.5 integers .
the item scores ranged from 0 to 8.5 , and the total score ranged from 0 to 18 ( table 2 ) .
the mean total severity scores in patients with df , dhf , and dss were 3.6  2.1 , 5.1  3.2 , and 11.0  4.1 ( table 3 ) .
the distribution of the derived severity scores was different among the three severity groups ( figure 1 ) .
the derived scores also discriminated dhf from df and also discriminated dss from dhf ( figure 2 ) .
our scoring system discriminated dss and dhf from df with an area under the receiver operation curve ( auroc ) of 0.7416 ( 95% ci = 0.72940.7537 , figure not shown ) and discriminated dss from dhf and df with a higher auroc of 0.8877 ( 95% ci = 0.87880.8964 , figure not shown ) .
cut - off points were assigned to classified patients as 3 severity groups : scores < 2.5 ( df ) , scores 2.511.5 ( dhf ) , and scores > 11.5 ( dss ) .
the score < 2.5 predicted df correctly in 297 out of 391 patients with 1-level underestimation in 149 patients ( 19.2% ) and 2-level underestimation in 5 patients ( 0.6% ) or a total of 19.8% underestimation .
the scores between 2.5 and 11.5 predicted dhf correctly in 136 out of 296 patients , with an underestimation in 46 patients ( 5.9% ) and an overestimation in 94 patients ( 12.1% ) .
the scores > 11.5 predicted dss correctly in 39 out of 90 patients , with 1-level overestimation in 1 out of 11 patients ( 1.4% ) , with no 2-level overestimation ( 0% ) , or a total of 1.4% overestimation ( table 3 ) .
dengue infection is an urgent condition requiring prompt diagnosis and treatment before patients enter into bleeding or shock states .
previous scoring systems trying to evaluate or forecast disease severity included the dengue fever scoring system based on epidemiological information and clinical signs or symptoms , which might be useful in detecting df very early prior to laboratory results .
other scoring systems were the pediatric logistic organ dysfunction ( pelod ) score and the pediatric risk of mortality iii ( prism iii ) , used to evaluate the mortality rates , and the disseminate intravascular coagulation ( dic ) score to diagnose dic and to discriminate df and dhf from other febrile illnesses .
decision tree algorithms were also applied to classify dengue infections into df , dhf grade i , dhf grade ii , and dhf grade iii .
they may also predict patients with low risk who may be discharged safely and select patients with high risk who should be admitted for close monitoring .
some studies included only adult patients [ 25 , 29 ] which may or may not be relevant for children . in studies which included children ,
some studies used information on the first few days of admission in pediatric intensive care unit ( picu ) . in some studies , included dhf patients did not experience shock and may not be inferred to patients with dss .
risk prediction in many studies was based on nonroutine laboratory investigations [ 19 , 20 , 26 , 28 , 29 ] . despite their high predictive powers ,
an investment on such facilities may not be feasible and may not be cost effective .
our study developed a scoring system based on clinical risk and routine laboratory parameters and categorized patients with dengue infection into df , dhf , or dss.patients scoring < 2.5 were classified as df which is the mildest form .
patients may safely be handled as outpatients with symptomatic treatments and may be advised to observe any abnormal signs or symptoms with a follow - up appointment.patients scoring between 2.5 and 11.5 were classified as a risk group for dhf .
these patients should be admitted to be closely monitored for early signs of plasma leakage , hemoconcentration , coagulopathy , thrombocytopenia.patients scoring > 11.5 were classified as a risk group for dss .
patients may safely be handled as outpatients with symptomatic treatments and may be advised to observe any abnormal signs or symptoms with a follow - up appointment .
these patients should be admitted to be closely monitored for early signs of plasma leakage , hemoconcentration , coagulopathy , thrombocytopenia .
our scoring system predicted dss correctly with a positive predictive value ( ppv ) of 88% , similar to other studies which reported a ppv of 8295% [ 20 , 26 ] .
however , the fact that the derived scores in df and dhf were more or less overlapping made it less likely to be used to differentiate dhf for df .
other nonroutine predictors specifically for dhf may be required . in case of continuous routine laboratory investigations
, our score may also be used to monitor the patients risk for dss as the disease progresses from day to day . in case of outpatients , this will help clinicians make decision when to admit the patients to hospital .
application of this scoring system into routine patient care may help reduce unnecessary admission and also reduce case facility in severe cases that are admitted based on high risk scores .
the derived dengue infection severity score classified patients into df , dhf , or dss , correctly into their original severity levels .
 
 objectives . to develop a simple scoring system to predict dengue infection severity based on patient characteristics and routine clinical profiles . 
 methods . 
 retrospective data of children with dengue infection from 3 general hospitals in thailand were reviewed . 
 dengue infection was categorized into 3 severity levels : dengue infection ( df ) , dengue hemorrhagic fever ( dhf ) , and dengue shock syndrome ( dss ) . 
 coefficients of significant predictors of disease severity under ordinal regression analysis were transformed into item scores . 
 total scores were used to classify patients into 3 severity levels . 
 results . 
 significant clinical predictors of dengue infection severity were age > 6 years , hepatomegaly , hematocrit 40% , systolic pressure < 90  mmhg , white cell count > 5000  /l , and platelet 50000  /l . 
 the derived total scores , which ranged from 0 to 18 , classified patients into 3 severity levels : df ( scores < 2.5 , n = 451 , 58.1% ) , dhf ( scores 2.511.5 , n = 276 , 35.5% ) , and dss ( scores > 11.5 , n = 50 , 6.4% ) 
 . the derived score correctly classified patients into their original severity levels in 60.7% . 
 an under - estimation of 25.7% and an over - estimation of 13.5% were clinically acceptable . conclusions . 
 the derived dengue infection severity score classified patients into df , dhf , or dss , correctly into their original severity levels . 
 validation of the score should be reconfirmed before application of routine practice . 
1. Introduction
2. Materials and Methods
3. Results
4. Discussions
5. Conclusions