Diagnosis delays associated with mortality among patients with haemorrhagic fever in Upper Southern Thailand: A hospital-based case control study

Abstract

Objective: To investigate the association between diagnosis delays and mortality in patients with haemorrhagic fever in Upper Southern Thailand.

Methods A hospital-based case control study was conducted between December 2019 and January 2020. Cases were defined as patients who had been diagnosed with haemorrhagic fever and died during hospitalization, while controls were patients with similar conditions who survived. Medical records were retrospectively reviewed, with the primary variable being a diagnosis delay of more than three days after the onset of illness. The outcome of interest was mortality during hospitalization. Data analysis involved descriptive statistics and multiple logistic regression.

Results A total of 38815 haemorrhagic fever cases were reported from 2014 to 2019. The case-to-control ratio was 1:3, comprising 66 cases and 198 controls. Among 66 cases and 198 controls, the median (IQR) time from illness onset to diagnosis was 4 (4) days in cases vs. 1 (0) day in controls. Diagnosis delays significantly increased mortality risk [adjusted OR (aOR) 5.60, 95% CI 2.74-11.46]. Other risk factors for mortality included age ≤5 years (aOR 16.15, 95% CI 3.70-70.42) and overweight status (aOR 3.43, 95% CI 1.57-7.52).

Conclusions Delayed diagnosis in patients with haemorrhagic fever was strongly associated with higher mortality rates. These findings highlight the critical importance of early diagnosis to reduce mortality in haemorrhagic fever cases.

Keywords

Diagnosis delays / Mortality / Haemorrhagic fever / Dengue haemorrhagic fever / Dengue shock syndrome

Conflict of interest statement

The authors declare no conflicts of interest.

Authors’ contributions

SC, BC, and SW conceptualized and designed the study. SC and SW collected the data and conducted the literature review, while SC and BC analyzed and interpreted the data. BC drafted the initial version of the manuscript, with input from SC and SW during the review and editing process. SW and BC supervised the project throughout. BC, as the guarantor, ensured the integrity of the work from its conception to the preparation of the manuscript. All authors have reviewed, approved, and endorsed the final version of the manuscript, affirming their confidence in the accuracy and integrity of the research.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

[1] World Health Organization. Dengue and severe dengue. [Online]. Available from: https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue. [Accessed on 24 January 2021].

[2] Kalayanarooj S. Dengue classification: Current vs. the newly suggested classification for better clinical application. J Med Assoc Thai 2011; 94(Suppl3): S74-S84.

[3] McFee RB. Selected mosquito borne illnesses-Dengue. Dis Mon 2018; 64(5): 246-274.

[4] World Health Organization, UNICEF. Handbook for clinical management of dengue. Geneva: World Health Organization; 2012.

[5] Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev 1998; 11(3): 480-496.

[6] Guzman MG, Alvarez M, Halstead SB. Secondary infection as a risk factor for dengue hemorrhagic fever/dengue shock syndrome: An historical perspective and role of antibody-dependent enhancement of infection. Arch Virol 2013; 158: 1445-1459.

[7] Suwanbamrung C, Le CN, Maneerattanasak S, Satien P, Kotchawat S, Nontapad O, et al. Developing and using a dengue patient care guideline for patients admitted from households to primary care units and the district hospital: A community participatory approach in Southern Thailand. One Health 2020; 10: 100168.

[8] Guo C, Zhou Z, Wen Z, Liu Y, Zeng C, Xiao D, et al. Global epidemiology of dengue outbreaks in 1990-2015: A systematic review and meta-analysis. Front Cell Infect Microbiol 2017; 7: 317.

[9] Department of Disease Control, Ministry of Public Health. Dengue. [Online]. Available from: https://ddc.moph.go.th/en/index.php. [Accessed on 12 August 2019].

[10] Office of Disease Prevention and Control 11, Nakhon Sri Thammarat, Thailand. Annual reports of surveillance 2018; 2019. [Online]. Available from: https://ddc.moph.go.th/odpc11/. [Accessed on 12 August 2019].

[11] Campbell KM, Lin CD, Iamsirithaworn S, Scott TW. The complex relationship between weather and dengue virus transmission in Thailand. Am J Trop Med Hyg 2013; 89(6): 1066.

[12] Ha TTN, Huy NT, Murao LA, Lan NTP, Thuy TT, Tuan HM, et al. Elevated levels of cell-free circulating DNA in patients with acute dengue virus infection. PloS One 2011; 6(10): e25969.

[13] Anders KL, Nguyet NM, Chau NVV, Hung NT, Thuy TT, Farrar J. Epidemiological factors associated with dengue shock syndrome and mortality in hospitalized dengue patients in Ho Chi Minh City, Vietnam. Am J Trop Med Hyg 2011; 84(1): 127-134.

[14] Moraes GH, de Fátima Duarte E, Duarte EC. Determinants of mortality from severe dengue in Brazil: A population-based case-control study. Am J Trop Med Hyg 2013; 88(4): 670-676.

[15] Chowell G, Diaz-Duenes P, Chowell D, Hews S, Ceja-Espíritu G, Hyman JM. Clinical diagnostic delays and epidemiology of dengue fever during the 2002 outbreak in Colima, Mexico. Dengue Bull 2007; 31: 26-35.

[16] Mallhi TH, Khan AH, Adnan AS, Sarriff A, Khan YH, Jummaat F. Clinico-laboratory spectrum of dengue viral infection and risk factors associated with dengue hemorrhagic fever: A retrospective study. BMC Infect Dis 2015; 15: 399. doi: 10.1186/s12879-015-1141-3.

[17] Nazish Butt NB, Amanullah Abbassi AA, Munir SM, Ahmad SM, Sheikh QH. Haematological and biochemical indicators for the early diagnosis of dengue viral infection. J Coll Physicians Surg Pak 2008; 18: 282-285.

[18] Kaewnorkkao V, Areechokchai D. Review of dengue death in epidemiological surveillance report, 2012. WESR Thailand 2013; 44: 209-213.

[19] Yatra IMS, Putra IWGAE, Pinatih GNI. Disease history and delayed diagnosis of dengue infection as risk factors for dengue shock syndrome in Wangaya Hospital Denpasar. Public Health Prev Med Arch 2015; 3(2): 188-193.

[20] Tauqeer Hussain Mallhi THM, Amer Hayat Khan AHK, Azmi Sarriff AS, Azreen Syazril Adnan ASA, Yusra Habib Khan YHK. Determinants of mortality and prolonged hospital stay among dengue patients attending tertiary care hospital: A cross-sectional retrospective analysis. BMJ 2017; 1136: 7(7): e016805. doi: 10.1136/bmjopen-2017-016805.

[21] Schlesselman JJ. Sample size requirements in cohort and case-control studies of disease. Am J Epidemiol 1974; 99(6): 381-384.

[22] Bernard R. Fundamentals of biostatistics. 5th ed. Duxbury: Thomson Learning; 2000.

[23] Fleiss JL, Levin B, Paik MC. Statistical methods for rates and proportions. 3rd ed. Hoboken, NJ: John Wiley & Sons; 2013.

[24] Ngamjarus C, Chongsuvivatwong V. McNeil E. n4Studies: Sample size and power calculations for an epidemiology study on a smart device. Siriraj Med J 2016; 68(3): 160-170.

[25] Consultation, WHO. Obesity: Preventing and managing the global epidemic. WHO Tech Rep Ser 2000; 894: i-xii,1-253.

[26] Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei ZG, et al. 2000 CDC growth charts for the United States: Methods and development. Vital Health Stat 2002; 11: 1-190.

[27] Mallhi TH, Khan AH, Sarriff A, Adnan AS, Khan YH. Patients related diagnostic delay in dengue: An important cause of morbidity and mortality. Clin Epidemiol Glob Health 2016; 4(4): 200-201.

[28] Kabra SK, Jain Y, Singhal T, Ratageri VH. Dengue hemorrhagic fever: Clinical manifestations and management. The Indian J Pediatr 1999; 66: 93-101.

[29] Nelwan EJ. Early detection of plasma leakage in dengue hemorrhagic fever. Acta Medica Indonesiana 2018; 50(3): 183.

[30] Widiyati MMT, Laksanawati IS, Prawirohartono EP. Obesity as a risk factor for dengue shock syndrome in children. Paediatri Indones 2018; 53(4): 187-192.

[31] Elmy S, Arhana BNP, Suandi IKG, Sidiartha IGL. Obesitas sebagai actor risiko sindrom syok dengue. Sari Pediatri 2016; 11(4): 238-243.

[32] Kurnia B, Suryawan IWB. The association between obesity and severity of dengue hemorrhagic fever in children at Wangaya general hospital. Open Access Maced J Med Sci 2019; 7(15): 2444-2446.

[33] Badawi A, Velummailum R, Ryoo SG, Senthinathan A, Yaghoubi S, Vasileva D, et al. Prevalence of chronic comorbidities in dengue fever and West Nile virus: A systematic review and meta-analysis. PLoS One 2018; 13(7): e0200200.

[34] Saqib MAN, Rafique I, Bashir S, Salam AA. A retrospective analysis of dengue fever case management and frequency of co-morbidities associated with deaths. BMC Res Notes 2014; 7: 205. doi: 10.1186/1756-0500-7-205.

[35] Pang J, Salim A, Lee VJ, Hibberd ML, Chia KS, Leo YS, et al. Diabetes with hypertension as risk factors for adult dengue hemorrhagic fever in a predominantly dengue serotype 2 epidemic: A case control study. PloS Neglect Trop Dis 2012; 6(5): e1641.