research article does comorbidity increase the risk of...

Hindawi Publishing CorporationISRN Tropical MedicineVolume 2013, Article ID 139273, 5 pageshttp://dx.doi.org/10.1155/2013/139273

Research ArticleDoes Comorbidity Increase the Risk of Dengue HemorrhagicFever and Dengue Shock Syndrome?

Shahid Mahmood,1 Saadia Hafeez,2 Hiba Nabeel,2 Urooj Zahra,2 and Hammad Nazeer3

1 Department of Community Medicine, Gujranwala Medical College, Gujranwala, Pakistan2 Fatima Jinnah Medical College, Lahore, Pakistan3 Department of Infectious Diseases, Shaukat KhanumMemorial Hospital, Lahore, Pakistan

Correspondence should be addressed to Shahid Mahmood; [email protected]

Received 18 June 2013; Accepted 24 July 2013

Academic Editors: P. A. Nogueira and M. A. Sosa

Copyright © 2013 Shahid Mahmood et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Background. Dengue fever is an emerging public health problem in Pakistan.The aim of this study was to determine the relationshipbetween comorbid conditions in individuals suffering from dengue fever and the development of dengue hemorrhagic fever ordengue shock syndrome. Methods. In this age- and sex-matched case control study, total of 132 cases of dengue hemorrhagicfever/dengue shock syndrome and 249 randomly selected controls were recruited from two major teaching hospitals of Lahore,Pakistan. A semistructured questionnaire was used to collect data through interview and by reviewing clinical records. SPSS version18 was utilized for statistical analysis including conditional logistic regression. Results. Odds of developing dengue hemorrhagicfever (DHF) and dengue shock syndrome (DSS) among diabetics are higher than in controls, but this association was not foundstatistically significant (OR. 1.26; 95% CI. 0.78–2.03; 𝑃 = 0.34). Similarly, no association was observed in individuals suffering fromhypertension (OR. 0.93; 95%CI. 0.57–1.49;𝑃 = 0.76). Odds of developingDHF andDSSwere higher for bronchial asthma (adjustedOR. 1.34) and pulmonary tuberculosis (adjusted OR. 1.41); however P values were insignificant. Conclusion. Presence of diabetesmellitus, hypertension, ischemic heart disease and bronchial asthma among patients contracted dengue fever will not increase therisk of dengue hemorrhagic fever and dengue shock syndrome.

1. Background

Dengue fever is an emerging public health problem prevalentmostly in tropical and subtropical regions of the world. Itis an arbovirus infection transmitted through Aedes aegyptiand Aedes albopictus mosquito species. Four dengue virusserotypes (DENV-1, DENV-2, DENV-3, and DENV-4) haveyet been identified and are responsible for most of theclinical manifestations, ranging from asymptomatic diseaseto symptomatic dengue fever (DF) and dengue hemorrhagicfever (DHF). Inmajority of patients, infection is self-limiting,but in small proportions, the resultant dengue shock syn-drome (DSS)may increasemorbidity andmortality. Infectionwith one serotype does not give protection against otherdengue viruses, yet sequential infections increase the riskof developing dengue hemorrhagic fever (DHF) and dengueshock syndrome (DSS) [1, 2].

Dengue is endemic in many Southeast Asian countriesandWestern pacific region [2]. About 2.5 billion people (40%of world’s population) are at risk of dengue transmission.The World Health Organization (WHO) estimates that 50 to100 million infections occur yearly, including 500,000 DHFcases and 22,000 deaths, mostly among children. Subjectswho developDHF have 3–5% chance of death if accompaniedby Dengue shock syndrome [2, 3]. In Pakistan, first dengueoutbreak was reported in Karachi during 1994 and sporadiccases occurred in coming years. Since environmental condi-tions are conducive to Aedes mosquito breeding in Pakistan,therefore dengue virus import through travelling and tradecompleted the disease transmission cycle. Economic andsecurity related migration 2004 onward introduced the virusin Lahore as well. According to Punjab health department,total of 590339 suspected cases of dengue were reportedin Lahore, out of which 21685 were confirmed by serology.

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The ratio of DF/DHF has not been reported; however it hasbeen observed that 5–10% of these cases developed DHF,whereas

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Table 1: Comorbidities in dengue hemorrhagic fever cases in comparison to control population.

Characteristics Cases (𝑛 = 132) Controls (𝑛 = 249) Total (𝑛 = 381) 𝜒2

𝑃-value𝑁 % 𝑁 % 𝑁 %

Age (years)

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Table 2: Risk of dengue hemorrhagic fever (DHF) in relation to existing comorbidities (𝑛 = 381).

Comorbidity Unadjusted estimates Adjusted estimates∗

OR. 95% CI. 𝑃 OR. 95% CI. 𝑃Diabetes mellitus

No 1 Reference 1 ReferenceYes 1.05 0.69–1.62 0.79 1.26 0.78–2.03 0.34

HypertensionNo 1 Reference 1 ReferenceYes 0.87 0.57–1.32 0.52 0.93 0.57–1.49 0.76

Ischaemic heart disease (IHD)No 1 Reference 1 ReferenceYes 1.14 0.66–1.95 0.62 1.52 0.85–2.73 0.15

Bronchial asthmaNo 1 Reference 1 ReferenceYes 1.16 0.57–2.34 0.66 1.34 0.62–2.88 0.44

Pulmonary tuberculosisNo 1 Reference 1 ReferenceYes 1.48 0.63–3.49 0.36 1.41 0.57–3.43 0.44

Duration of diabetes Mellitus10 years 1.44 0.58–3.59 0.42 1.86 0.55–6.26 0.31

Duration of hypertension10 years 1.25 0.42–3.56 0.71 0.73 0.14–3.66 0.70

∗Adjusted for age, sex, and duration of illness.

to screen patient at early stage for monitoring and earlyintervention. This study was initiated on a premise thatcertain comorbidities might increase the risk of developingdengue hemorrhagic fever (DHF) and dengue shock syn-drome (DSS).This premisewas based on clinical observationscommunicated by clinicians at various forums. In order totest this hypothesis, patients of DHF/DSS were comparedwith those who only had dengue fever for presence ofcomorbidities like cardiovascular diseases, diabetes mellitus,chronic liver disease, chronic lung disorders and allergies.We did not find any statistical association with these comor-bidities, though unadjusted estimates suggest that individualssuffering from diabetes mellitus and ischemic heart diseaseshave higher odds of developing DHF than the controlpopulation. Similar observation was also reported by Riaz etal. [10] that the diabetics were at higher risk of DHF thanthe control population. Similarly, of the 170 cases of DHFand 1175 controls in their study, Figueiredo et al. [11] foundthat individuals who reported allergies and taking steroids;those who had diabetes were 2.5 times at higher risk ofdeveloping DHF. Adjusted odds ratio in the mentioned studyfor diabetes was 2.75 (95% CI. 1.12–6.73) and that for allergieswas 1.29 (95% CI. 0.87–1.89). In contrast, though adjustedodds ratio in our case was 1.26; however wide confidenceinterval (0.78–2.03) and insignificant P-value indicates theeffect of smaller sample size used in our study. As regards

hypertension and ischemic heart disease, we did not findany association and these findings were consistent withstudies in Brazil and Puerto Rico [12]. Duration of illness incase of diabetes mellitus was significant (OR. = 2.76 for 5–10 years of illness), yet no such relationship was observedfor hypertension. Although, no statistical association wasobserved between chronic lung issues like tuberculosis andbronchial asthma, however, other studies did found positiverelationship between allergies and DHF [11]. We cannotcomment on this issue as none of our participant reportedhistory of allergies; nevertheless considering close associationbetween allergies and bronchial asthma, such link cannot beignored.

Results of this study should be interpreted consider-ing its retrospective nature, issues related to incompleteclinical data available, and relatively small control popula-tion for comparison. Moreover, results may lack externalvalidity since the cases were recruited mainly from threemajor hospitals in Lahore and did not include patientsin private clinics. Considering the strong evidence pro-vided by studies in Brazil and Puerto Rico [12] aboutrelationship between comorbidities and development ofdengue hemorrhagic fever, we suggest a followup study withlarger comparison group in order to screen those denguecases with tendency to progress to dengue hemorrhagicfever.

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5. Conclusion

This is probably the first study in Pakistan to investigate therelationship between dengue hemorrhagic fever and selectedcomorbid conditions. We did not find any statistical associ-ation between dengue hemorrhagic fever and dengue shocksyndrome with diabetes mellitus, hypertension, bronchialasthma, chronic lung disease, and chronic liver diseases.

Conflict of Interests

The authors declare no competing interests. There was noexternal funding involved for any part of this study.

Authors’ Contribution

Shahid Mahmood contributed in study conception, design,data analysis and interpretation, and drafting the paper.Saadia Hafeez helped in study design, data collection, anddrafting the paper. Hiba Nabeel participated in data col-lection, data management, and drafting tables. Urooj Zahrahelped in data collection, paper revision, and final drafting.Hammad Nazeer helped in study design, interpretation ofresults, and revision of the paper. All the authors read andapproved the final manuscript for publication.

Acknowledgments

The authors are grateful to all subjects and their relativesfor sparing precious time for interview and allowing reviewof clinical records. The authors also would like to thankthe cooperation and facilitation of all the medical andparamedical staff of Sir Ganga Ram and Jinnah Hospitals.

References

[1] World Health Organization, Dengue and Dengue Haemmor-rhagic Fever, World Health Organization, Geneva, Switzerland,2012.

[2] Centers for Disease Control (CDC), “Epidemiology of Denguefever,” 2012, http://www.cdc.gov/dengue/epidemiology/index.html.

[3] M. Malik, “Dengue prevention, control and management,”in International Conference in Lahore Pakistan on DenguePrevention and Management, 2012.

[4] J. A. Potts and A. L. Rothman, “Clinical and laboratory featuresthat distinguish dengue from other febrile illnesses in endemicpopulations,” Tropical Medicine and International Health, vol.13, no. 11, pp. 1328–1340, 2008.

[5] D. J. Gubler, “Epidemic dengue/dengue hemorrhagic fever as apublic health, social and economic problem in the 21st century,”Trends in Microbiology, vol. 10, no. 2, pp. 100–103, 2002.

[6] L. Thomas, Y. Brouste, F. Najioullah et al., “Predictors of severemanifestations in a cohort of adult dengue patients,” Journal ofClinical Virology, vol. 48, no. 2, pp. 96–99, 2010.

[7] G. N. Malavige, P. K. Ranatunga, V. G. N. S. Velathanthiri et al.,“Patterns of disease in Sri Lankan dengue patients,” Archives ofDisease in Childhood, vol. 91, no. 5, pp. 396–400, 2006.

[8] J. G. Rigau-Pérez and M. K. Laufer, “Dengue-related deaths inPuerto Rico, 1992–1996: diagnosis and clinical alarm signals,”Clinical Infectious Diseases, vol. 42, no. 9, pp. 1241–1246, 2006.

[9] O. Parkash, A. Almas, S. W. Jafri, S. Hamid, J. Akhtar, and H.Alishah, “Severity of acute hepatitis and its outcome in patientswith dengue fever in a tertiary care hospital Karachi, Pakistan(South Asia),” BMC Gastroenterology, vol. 10, no. 2, article 43,2010.

[10] M. M. Riaz, K. Mumtaz, M. S. Khan et al., “Outbreak of denguefever in Karachi 2006: a clinical perspective,” Journal of thePakistan Medical Association, vol. 59, no. 6, pp. 339–344, 2009.

[11] M. A. A. Figueiredo, L. C. Rodrigues, M. L. Barreto et al.,“Allergies and diabetes as risk factors for dengue hemorrhagicfever: results of a case control study,” PLoS Neglected TropicalDiseases, vol. 4, no. 6, article e699, 2010.

[12] J. G. Rigau-Pérez and M. K. Laufer, “Dengue-related deaths inPuerto Rico, 1992–1996: diagnosis and clinical alarm signals,”Clinical Infectious Diseases, vol. 42, no. 9, pp. 1241–1246, 2006.

[13] World Health Organization, “Impact of dengue,” 2008,http://www.who.int/csr/disease/dengue/impact/en/index.html.

[14] World Health Organization, “Comprehensive guidelines forprevention and control of Dengue and Dengue haemorrhagicfever- Revised and expanded edition, 2011,” SEARO technicalpublication series No. 60, http://www.searo.who.int/entity/vec-tor borne tropical diseases/documents/SEAROTPS60/en/in-dex.html.

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