The Warning Signs And Impact Factors Of Severe Dengue In China

Dengue fever (DF) is an acute febrile infectious disease caused bydengue virus infection and transmitted by infected mosquito. Dengue viruscan be subdivided into four major serotypes (DENV-1, DENV-2, DENV-3andDEN-4). A wide variety of clinical manifestations may occur after denguevirus infected，ranging from mild febrile illness to severe and fataldisease. Its severe form like dengue hemorrhagic fever and dengue shocksyndrome resulted in approximately20,000deaths every year. Dengue feverhas become an important disease which impacted public health in developingcountries. Dengue epidemic mainly along the coast area in China,especially in Guangdong province, where dengue has been reported almostevery year. Early diagnosis and treatment timely is the key to cure severedengue fever and reduce the mortality. For help emerging healthcaresevices better cope with explosive dengue outbreaks, World HealthOrganization (WHO) published the dengue guidelines for diagnosis,treatment, prevention and control in2009, proposed a revised andsimplified classification of DF into dengue fever (D) and severe dengue(SD). With an intermediary group of “dengue with waning signs (DWS)”,andsuggesting seven warning signs to identify patients at risk of SD, theproposed warning signs include abdominal pain or tenderness, persistentvomiting, clinical fluid accumulation, mucosal bleed, lethargy orrestlessness, liver enlargement>2cm, increase in hematocrit concurrent with rapid decrease in platelet count. The classification has been testedand validated in a lot of studies in endemic regions. The conclusion ofthe studies was that the acceptance in relation to case management washigh. However, there is ongoing discussion in literature on the relativeusefulness and applicability of the new classification. To date, no studyon applying the new classification has been performed in china. Therefore,it is significant to investigate the clinical and laboratory marker forsevere dengue in China. The project is of highly importance forestablishing dengue guiedlines of diagnosis and treatment applicable forour country, and will improve the dengue case management in China and helpto consummate the present WHO criteria for dengue.To date, The factorsresulting in severe dengue are still not clear, which has hampered theclinical management of severe dengue case. Individual risk factors maybedetermine the severity of disease and include age, gender, possiblychronic diseases, and secondary infection. Analysis of severe dengue casebased on clinical data, serological and virological tests will providereliable evidences in pathogenesis and impact factors leading to severedengue.Objects1. To summarize the clinical and experimental characteristics of denguefever patients in our country.And to validate the utility of warning signsand diagnostic criteria from the WHO2009guideline.2. To analyze the characteristics of clinical and etiology of the firstconfirmed case of severe dengue fever cases in mainland China，and clarifythe pathogenesis and impact factors leading to severe dengue.Research Methods1. Retrospective analyzed clinical and laboratory data of the dengue feverpatients who hospitalized in Guangzhou No.8People’s Hospital from1990 to2012, and deal the data with Clinical Data Analysis And ManagementInformation System;2. Retrospective analyzed the clinical and laboratory characteristics ofthe severe dengue fever cases.3. Dengue virus specific IgM and IgG antibody were detected in acute phaseand convalescence phase serum of patient by enzyme linked immolunosorbentassay (ELISA). The neutralizing antibodies against all four serotypes ofDENV were detected by plaque reduction neutralization test (PRNT) in acutephase and convalescence phase serum.4. Total RNA was extracted from acute phase serum of patient.Then ccordingto the WHO new guidelines for dengue, universal dengue primers targetingthe C/prM region of the genome were used for an initial reversetranscription and amplification step, followed by a nested PCRamplification that is serotype-specific. Using PCR DESIGN software, Egene of the genome was amplified, and phylogenetic analysis based on thenucleic acid sequence of the complete E gene of29DENV-1was carried outby Neighbor-Joining method to determine the origin of infected denguevirus.Results1. There were1896cases hospitalized in Guangzhou No.8People’s Hospitalbetween1990to2012. Of these patients,1647aged>18years old (88.3%).Dengue fever (DF) occurred in1890cases, Dengue hemorrhagic fever (DHF)occurred in5cases，Dengue shock syndrome (DSS) occurred in1case.According to the WHO2009diagnostic criteria, Dengue fever without waringsigns (WS) occurred in1262cases, Dengue fever with WS occurred in496cases, SD occurred in138cases. Of the138SD patients,18(13.0%) patientsdeveloped shock,6(4.3%) developed fluid accumulationwith respiratorydistress.77(55.8%) developed severe bleeding.5(3.6%) developed ALT/AST>1000U/L.4(2.9%) developed inpaired consciousness.31(22.5%)developed myocarditis.11(8.0%) developed renal insufficiency.2. Of these cases, waring sign occurred in634cases. The commonest warningsigns were lethargy (28.5%), clinical fluid accumulation (15.7%) andmucosal bleeding (27.1%). Specificity was>90%for SD with abdominal painor tenderness (97.3%), hepatomegaly (99.8%), hematocrit rise and rapidplatelet drop (99.5%).3. The first case of severe dengue in China is a68-year-old female patient,with a history of diabetes and chronic renal insufficiency for severalyears. She was with complaints of fever, headache, arthralgia, ecchymosisand gastrointestinal tract bleeding. Significant laboratory findingsincluded leukopenia, thrombocytopenia, liver and renal functionimpairments, and decreased albumin. On abdominal ultrasonic examination,gall bladder thickening was observed.4. Virological tests and phylogenetic analysis demonstrated this case ofsevere dengue was caused by DENV-1.We named the dengue virus as GZ63,plylogenetic analysis using the Neighbor-Jonining method revealed thatGZ63fell into genotype I with close relationship with isolates fromSoutheast Asia.5. Serologicl tests suggested that this case was caused by the secondarydengue virus infection, and the primary dengue virus was DENV-2.Conclusion1. In our cohort,138cases were classified as SD. Cases classified asSD had more severe illness than DF cases. It proved the utility of thenew WHO guildline. Abdominal pain or tenderness, hepatomegaly, clinicalfluid accumulation and hematocrit rise and rapid platelet count drop werehighly specific for SD.2. Age, female, complicated with hypertension and diabetes mellitus,secondary infected with DENV were the factors inducting SD in the case. Gall bladder thickening observed by Color B-Ultrasonic maybe a sign todiagnose severe dengue in early stage of illness.