Objective: To compare the original (1997) and revised (2009) versions of World Health Organization guidelines for dengue patientsMethods: Adult patients with a positive dengue Immunoglobulin M serology, and a diagnosis of dengue were included in the study at Aga Khan University Hospital during a three-year period from January 2005 to December 2007. Data related to these dengue patients was collected from their medical records. Guidelines were then applied by the research assistant and correlation among these guidelines was computed. SPSS 19 was used for statistical analysis.Results: A total of 612 patients were found with a diagnosis of dengue, but only 439 (71.73%) had a positive IgM. The median age of these 439 patients was 28 (interquartile range: 18) years and majority of them were males, 295 (67%). According to the 1997 guidelines, 383 (87%) patients were classified as having dengue, while according to the 2009 guidelines, all the 439 (100%) patients were classified with a dengue infection. Under WHO 1997, 21 (5.5%) cases were classified as dengue shock syndrome, while 2009 guidelines labelled 88 (20%) cases as severe dengue. There was a consensus on only 11 severe cases by both the guidelines, showing different results between the two.Conclusion: By using 2009 guidelines, a physician would classify more dengue patients as having severe disease

Ejaz, Kiran

Fayyaz, Jabeen

Khan, Uzma R.

Khursheed, Munawar

Qamar, Irum

Razzak, J.

eCommons@AKU

eCommons@AKUDepartment of Emergency Medicine Medical College, PakistanJune 2013A comparison of WHO guidelines issued in 1997and 2009 for dengue fever - single centreexperience.Munawar KhursheedAga Khan University, munawar.khursheed@aku.eduUzma R. KhanAga Khan University, uzma.khan@aku.eduKiran EjazAga Khan UniversityJabeen FayyazAga Khan UniversityIrum QamarAga Khan UniversitySee next page for additional authorsFollow this and additional works at: http://ecommons.aku.edu/pakistan_fhs_mc_emerg_medPart of the Infectious Disease Commons, and the Parasitic Diseases CommonsRecommended CitationKhursheed, M., Khan, U., Ejaz, K., Fayyaz, J., Qamar, I., Razzak, J. (2013). A comparison of WHO guidelines issued in 1997 and 2009for dengue fever - single centre experience.. Journal of Pakistan Medical Association, 63(6), 670-674.Available at: http://ecommons.aku.edu/pakistan_fhs_mc_emerg_med/57AuthorsMunawar Khursheed, Uzma R. Khan, Kiran Ejaz, Jabeen Fayyaz, Irum Qamar, and J. RazzakThis article is available at eCommons@AKU: http://ecommons.aku.edu/pakistan_fhs_mc_emerg_med/57IntroductionDengue infection is caused by Flavivirus and spreadsthrough Aedes aegypti mosquito. The virus infects over 50million people worldwide, resulting in over 24,000 deathsannually.1,2 Billions of people remain exposed to thedisease across Africa, Eastern Mediterranean, SoutheastAsia and Western Pacific region.3Clinical presentation of patients with dengue infectionvaries from a self-limiting, non-specific acute febrile illnessto a syndrome characterised by bleeding, severeintravascular volume depletion and shock.4 Given itsvague presentation, early identification of severeinfections can be challenging, causing delays in theinstitution of life-saving interventions. To assist cliniciansin making triage decisions, the World Health Organisation(WHO) published a dengue infection triage and treatmentguideline in 1997.5 It was based on the data frompaediatric population of Bangkok and divided the clinicalsyndrome into dengue fever (DF), dengue haemorrhagicfever (DHF) and dengue shock syndrome (DSS).6-8 Arevised version of the guideline was published in 2009 toaddress the low sensitivity in high-risk patients and wasmore inclusive of adult patients as well.2,9,10 The newclassification, while retaining the three-level severitygrading, divided the infection into dengue withoutwarning signs, dengue with warning signs and severedengue.2,6,10Pakistan has experienced a major epidemic of dengueinfection since 2005.11 Hospitals, especially theemergency departments (ED), have seen a major surge inthe dengue patient volume. In the beginning of theepidemic, triage decisions were based on the clinician'sjudgment, while WHO guidelines were slowly beingaccepted as the decision-making tool. Recently publishedstudies from other settings have shown better accuracy ofthe revised guidelines.2,12,13 This study was carried out tocompare the performance of 1997 and 2009 WHOguidelines based on the dengue Immunoglobulin (IgM)results in our setting.2,5Patients and MethodsThis was a case series of Dengue patients recruited byretrospective chart review conducted at the Aga KhanUniversity Hospital (AKUH) Karachi, Pakistan. All adultpatients with a diagnosis of dengue who had a positivedengue IgM serology between January 2005 andDecember 2007 were included in the study. Cases withincomplete information such as signs, symptoms andJ Pak Med Assoc670ORIGINAL ARTICLEA comparison of WHO guidelines issued in 1997 and 2009 fordengue fever — single centre experienceMunawar Khursheed, Uzma Rahim Khan, Kiran Ejaz, Jabeen Fayyaz, Irum Qamar, Junaid Abdul RazzakAbstractObjective: To compare the original (1997) and revised (2009) versions of World Health Organization guidelines fordengue patientsMethods: Adult patients with a positive dengue Immunoglobulin M serology, and a diagnosis of dengue wereincluded in the study at Aga Khan University Hospital during a three-year period from January 2005 to December2007. Data related to these dengue patients was collected from their medical records. Guidelines were then appliedby the research assistant and correlation among these guidelines was computed. SPSS 19 was used for statisticalanalysis.Results: A total of 612 patients were found with a diagnosis of dengue, but only 439 (71.73%) had a positiveIgM. The median age of these 439 patients was 28 (interquartile range: 18) years and majority of them weremales, 295 (67%). According to the 1997 guidelines, 383 (87%) patients were classified as having dengue, whileaccording to the 2009 guidelines, all the 439 (100%) patients were classified with a dengue infection. UnderWHO 1997, 21 (5.5%) cases were classified as dengue shock syndrome, while 2009 guidelines labelled 88 (20%)cases as severe dengue. There was a consensus on only 11 severe cases by both the guidelines, showingdifferent results between the two.Conclusion: By using 2009 guidelines, a physician would classify more dengue patients as having severe disease.Keywords: Pakistan, Dengue, WHO guidelines. (JPMA 63: 670; 2013)Department of Emergency Medicine, Aga Khan University, Karachi, Pakistan.Correspondence:Munawar Khursheed. Email: munawar.khursheed@aku.edulaboratory figures were excluded. By using a standardtool, trained research assistants extracted dataregarding clinical features, laboratory investigations,on-admission diagnosis in ED and diagnosis of hospitalwith serological test (IgM anti-dengue). In our currentclinical setting, we send dengue IgM test on allsuspicious patients. Anti-IgM becomes positive onthe fifth day of dengue illness and can remainpositive for 90 days.No patient had polymerase chain reaction (PCR) testor culture of the virus. Each patient wasclassified/graded both according to 1997 (DengueFever, Dengue Haemorrhagic Fever and DengueShock Syndrome) and 2009 guidelines (denguewithout warning signs, dengue with warning signsand severe dengue) (Table-1, Figure-1) by theresearch assistant using the standard definitions. Thethree categories of dengue used in each of theVol. 63, No. 6, June 2013A comparison of WHO guidelines issued in 1997 and 2009 for dengue fever — single centre experience 671Table-1: WHO guidelines (1999) for the treatment of dengue fever/ dengue hemorrhagic fever.DF/DHF Grade* Symptoms Laboratory pictureDF Fever with two or more of the following signs: Leukopenia occasionally. Thrombocytopenia may be headache, retro -orbital pain, myalgia, arthralgia present. No evidence of plasma lossDHF I Above signs plus positive tourniquet test Thrombocytopenia positive tourniquet < 100,000, Hct rise > 20%DHF II Above signs plus spontaneous bleeding Thrombocytopenia < 100,000, Hct rise > 20%DHF III Above signs plus circulatory failure (weak pulse, hypotension restlessness) Thrombocytopenia < 100,000, Hct rise > 20%DHF IV Profound shock with undetectable blood pressure and pulse Thrombocytopenia < 100,000, Hct rise > 20%DHF Grade III and IV are also called as Dengue Shock Syndrome (DSS).Figure-1: Dengue, guidelines for diagnosis, treatment, prevention and control new edition 2009.guidelines were referred to as minor, moderate andsevere. Minor dengue was used for DF (1997guidelines) and dengue without warning signs (2009guidelines); moderate dengue for DHF (1997) anddengue with warning signs (2009); and severe denguefor DSS (1997) and severe dengue (2009).Descriptive analysis was done using SPSS, version 19.0and frequencies and percentages were calculated.Median with interquartile range (IQR) was reported forskewed data such as age and platelet count, while mean ±standard deviation (SD) was used for normal data. Ethicalapproval was obtained from the institutional ethicsreview committee.ResultsA total of 612 patients were located with a diagnosis ofdengue out of which 439 (71.73%) had a positive IgM.According to 1997 guidelines, 383 (87%) patients wereclassified as having dengue. On the other hand, 2009guidelines classified 439 (100%) patients as dengueinfected (Figure-2). Of the 56 (13%) cases which could notbe labelled as dengue using the 1997 guidelines, 30 (54%)were classified as probable dengue without warningsigns, 19 (34%) were classified as dengue with warningsigns, and 7 (12%) as severe dengue using the 2009guidelines.The median age of the participants was 28 (IQR 18) years;295 (67%) were males. All patients were discharged fromthe hospital except one patient who died in the hospital.Only 167v(38%) patients had three or more symptoms onhistory. Most (n=248; 56%) had no signs on examination(Table-2). All the patients presented with fever (100%),vomiting 281 (64%) and body ache 173 (39%). Rash (27%),petechiae (10%) and purpura (1%) were present in lessnumber of patients.Table-3 shows the comparison of both guidelines. Thetwo guidelines classified approximately 50% of casessimilarly as minor, moderate and severe dengue (Table-2).WHO 1997 had classified 21 (5.5%) cases as DSS while2009 guidelines labelled 81 (21%) cases as severe dengue,with consensus on only 11 (52.4%) severe cases by boththe guidelines. The alarming result was that more than aquarter cases (29%) that were classified as moderate bythe 1997 guideline were severe dengue according to the2009 guidelines. J Pak Med Assoc672 M. Khursheed, U. R. Khan, K. Ejaz, et al.Table-2: Clinical features of study population (n = 439).Clinical Symptoms n(%)Fever 439 (100)Vomiting 281(64)Body ache 173(39)Abdominal pain 152(35)Bleeding other than nose and gum 75(17)Headache 35(8)Gum Bleed 32(7)Nose Bleed 26(5)Haematemesis 22(5)Drowsiness 21(5)Shortness of Breadth 14(3)Examination Findings n(%)Rash 120(27)Ascites 44(10)Petechie 45(10)Hepatomegaly 19(4)Pulmonary Effusion 16(4)Splenomegaly 9(2)Purpura 6(1)Vital Examination Readings Mean ± SDTemperature(oC) 38±3Systolic Blood Pressure(mm Hg) 112±17Diastolic Blood Pressure(mm Hg) 72±12Pulse Pressure(beats/min) 40±14Laboratory Parameters Mean ± SDWhite Blood Count(x109/L)(n=431) 5±4Haematocrit(gm/dl)(n=426) 41±7Prothrombin Time(secs)(n=362) 13±8International Normalized Ratio(n=359) 1±2Activated Partial Thromboplastin Time(secs)(n=367) 37±20Sodium(mEq/L)(n=406) 138±75Bicarbonate(mEq/L)(n=332) 22±5M e d i a n(IQR)Platelet(x109/L)(n=427) 45(67)Blood Urea Nitrogen(mg/dL)(n=368) 9(6)Creatinine(mg/dL)(n=409) 1(0.4)Serum Glutamate-Oxaloacetate Transaminase(units/L)(n=388) 174(274)Table-3: Comparison of WHO guidelines for dengue cases (n=383).Disease Severity Disease Severity as per 2009 Classificationas per 1997 Dengue Fever Dengue Haemorrhagic Dengue Shock TotalClassification n(%) Fever n(%) Syndrome n(%) n(%)Probable Dengue without warning signs 68 (45.3) 48(22.6) 4(19) 120(31.3)Probable Dengue with warning signs 73(48.7) 103(48.6) 6(28.6) 182(45.7)Severe dengue 9(6) 61(28.8) 11(52.4) 81(21.1)Total 150(100) 212(100) 21(100) 383(100)DiscussionWe not only found a difference between 1997 and 2009guidelines in the accuracy of dengue diagnosis, but alsoin the assessment of the severity of the disease.2,5 Therewas a four-fold increase in the diagnosis of severe form ofdengue using 2009 guidelines compared to the 1997guidelines.The diagnostic challenge is likely to be higher in oursetting where other febrile illnesses are more common.Diseases such as typhoid fever or malaria contribute to amajor bulk of acute clinical practice in Pakistan and, likedengue, they often present with non-specific fever, fewsigns or symptoms and a blood picture showing lowwhite blood cell (WBC) and platelet counts.14.15 Atypicalpresentations such as abdominal pain, vomiting,diarrhoea, cough and headache resembling enteric feverhave been reported in other studies from Pakistan,making clinical decision more difficult.16 In such endemicsettings, concurrent infections such as dengue andmalaria could mislead physician's initial impression.Coexistence of malaria and dengue have been reported tobe in the range of 20% to as high as 80%.17,18 Whilemalaria testing is more widely available, diagnostic testsfor dengue (IgM) are either not available or not able todetect dengue in the first few days of the disease onset,biasing the clinical diagnosis towards malaria.Patients in our setting tend to start the use of antibioticand other medicines either in consultation with a generalphysician or by themselves. In Pakistan, there are no strictprescription regulations and drugs are easily availableover the counter. Patients visit the hospital only whentheir condition deteriorates, and this makes correctdiagnosis challenging for the physicians. Time also affects accuracy of diagnosis even when WHOguidelines are used. Leo et al reported an increase in theaccuracy of diagnosis by the WHO guidelines from 14% to32% and 61% to 79% from day 1 to day 7 of admissionusing the 1997 and 2009 guidelines respectively.13 Astudy from Karachi, showed that almost one-fourth ofchildren with final diagnosis of DF were initially labelled asundifferentiated fever.19 Similarly, in Vietnam about a thirdof cases with DF were initially diagnosed as acuteundifferentiated fever.20Revised guidelines were found to be better in diagnosingdengue cases overall, particularly those with severe formof illness. This is corroborated by work done in othersettings, both among adults and children.12,21 DENCO, aVol. 63, No. 6, June 2013A comparison of WHO guidelines issued in 1997 and 2009 for dengue fever — single centre experience 673Figure-2: Flow chart of dengue patients recruitment (January 2005- December 2007).multi-country prospective study, found comparableresults where 15% of patients with clinical shock were notcorrectly classified by 1997 classification as severe cases.22One reason is, perhaps, paediatric focus of the 1997guidelines which limited its application to adultpopulation.7,9,23 The 2009 classification included morenon-specific alarming signs such as mental statuschanges, abdominal pains and involvement of otherorgans such as liver. The current study has several limitations. First, it is basedon the retrospective data obtained from medical records.Not all features, for example, tourniquet test, wereuniversally captured in the medical records. Second, wecould not include dengue patients who weremisdiagnosed and sent home and also those who weresent home because they had mild disease.24 Third, we didnot know if the individual physician applied theguidelines or was even aware of the guidelines.ConclusionBy using the WHO guidelines 2009, a physician would endup classifying more dengue patients as having moderateor severe disease compared to the 1997 guideline.Widespread use of these guidelines needs to beencouraged among physicians.Acknowledgements We are thankful to Mr. Iqbal Azam for statistical help andDr. Rehan Nasir and Dr. Munira Abdul Aziz for helping indata collection. Authors URK and JAR were partiallysupported through the "Johns Hopkins-PakistanInternational Collaborative Trauma and Injury ResearchTraining Program", Grant Number D43-TW007-292 fromthe Fogarty International Center of the United StatesNational Institutes of Health.References1. Gibbons RV, Vaughn DW. Dengue: an escalating problem. BMJ 2002;324: 1563-6. 2. TDR, WHO. Dengue: guidelines for diagnosis, treatment, preventionand control.  New Edition. Geneva: WHO. 2009.3. Singhasivanon P, Jacobson J. Dengue is a major global healthproblem. Foreword.  J Clin Virol 2009; 46 suppl 2: S1-2.4. Guzman MG, Vázquez S, Kouri G. Dengue: where are we today?Malays J Med Sci 2009; 16: 4-11.5. Dengue haemorrhagic fever: diagnosis, treatment, prevention andcontrol. 2nd edition. Geneva: WHO . 1997.6. World Health Organization. Guidelines for treatment of denguefever / dengue hemorrhagic fever in small hospitals WHOregional office for South-East Asia, New Dehli. Dengue BulletinVolume 23. 1999. 1-23.7. Gupta P, Khare V, Tripathi S, Nag VL, Kumar R, Khan MY, et al.Assessment of World Health Organization definition of denguehemorrhagic fever in North India. J Infect Dev Ctries 2010; 4: 150-5..8. Bandyopadhyay S, Lum LC, Kroeger A. Classifying dengue: a reviewof the difficulties in using the WHO case classification for denguehaemorrhagic fever. Trop Med Int Health 2006; 11: 1238-55. 9. Rigau-Pérez JG. Severe dengue: the need for new case definitions.Lancet Infect Dis  2006; 6: 297-302.10. Research SPf, Diseases TiT, Diseases WDoCoNT, Epidemic WHO, AlertP. Dengue: Guidelines for diagnosis, treatment, prevention andcontrol World Health Organization 2009.11. Khan E, Kisat M, Khan N, Nasir A, Ayub S, Hasan R. Demographic andclinical features of dengue fever in Pakistan from 2003-2007: aretrospective cross-sectional study. PLoS One. 2010; 5: e12505.Published Online First: 13 September 2010. doi:10.1371/journal.pone.0012505 (accessed on ... )12. Basuki PS, Budiyanto, Puspitasari D, Husada D, Darmowandowo W,Ismoedijanto, et al. Application of revised dengue classificationcriteria as a severity marker of dengue viral infection in Indonesia.Southeast  Asian J Trop Med Public Health 2010; 41: 1088-94. .13. Leo YS, Thein TL, Fisher DA, Low JG, Oh HM, Narayanan RL, et al.Confirmed adult dengue deaths in Singapore: 5-year multi-centerretrospective study. BMC Infect Dis 2011; 11: 123. Published OnlineFirst: 12 May 2011. doi: 10.1186/1471-2334-11-123.14. Potts JA, Rothman AL. Clinical and laboratory features thatdistinguish dengue from other febrile illnesses in endemicpopulations. Trop Med Int Health 2008; 13: 1328-40. PublishedOnline First: 18 September 2008. doi: 10.1111/j.1365-3156.2008.02151.x.15. Shahid M, Razzak J, Jamali S, Ali SS, Ayubi TK. Initial diagnosticcategories of patients presenting to four major emergencydepartments in Karachi. J Coll Physicians Surg Pak 2006; 16: 680.16. Sudjana P, Jusuf H. Concurrent dengue hemorrhagic fever andtyphoid fever infection in adult: case report. Southeast Asian J TropMed Public Health 1998; 29: 370-2.17. Ali N, Nadeem A, Anwar M, Tariq WU, Chotani RA. Dengue fever inmalaria endemic areas. J Coll Physicians Surg Pak 2006; 16: 340-2. 18. Abbasi A, Butt N, Sheikh QH, Bhutto AR, Munir SM, Ahmed SM.Clinical features, diagnostic techniques and management ofdual dengue and malaria infection. J Coll Physicians Surg Pak2009; 19: 25-9. 19. Siddiqui FJ, Haider SR, Bhutta ZA. Endemic dengue fever: a seldomrecognized hazard for Pakistani children. J Infect Dev Ctries 2009; 3:306-12. 20. Phuong H, de Vries PJ, Nga TTT, Giao PT, Hung LQ, Binh TQ, et al.Dengue as a cause of acute undifferentiated fever in Vietnam. BMCInfect Dis. 2006; 6: 123. Published Online First: 25 July 2006.doi:10.1186/1471-2334-6-12321. Balmaseda A, Hammond SN, Perez MA, Cuadra R, Solano S, Rocha J,et al. Short report: Assessment of the World Health Organizationscheme for classification of dengue severity in Nicaragua. Am J TropMed Hyg 2005; 73: 1059-62.22. Martínez -Torres E. Dengue. Estudos avançados. 2008; 22: 33-52.http://dx.doi.org/10.1590/S0103-4014200800030000423. Rigau-Pérez J. Severe dengue: the need for new case definitions.Lancet Infect Dis 2006; 6: 297-302.24. Guzman MG, Kouri G. Dengue diagnosis, advances and challenges.Int J Infect Dis 2004; 8: 69-80.J Pak Med Assoc674 M. Khursheed, U. R. Khan, K. Ejaz, et al.

A comparison of WHO guidelines issued in 1997 and 2009 for dengue fever - single centre experience.

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A comparison of WHO guidelines issued in 1997 and 2009 for dengue fever - single centre experience.

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