Abstract
Introduction:
Dengue fever is a common mosquito-borne viral disease which has reached alarming size in the past few years. It is endemic in more than 100 countries and significant differences were found in clinical profile and atypical manifestation.
Aim of the Study:
A retrospective observational study of clinical profile and atypical manifestations in patients with dengue fever.
Materials and Methods:
Serum samples were collected from clinically suspected cases of dengue fever and it was confirmed by NS1 antigen, IgM, and IgG antibody by ELISA. Clinical details and atypical manifestations were recorded.
Observation:
During the study period, a total of 2502 patients were suspected to have dengue infection, of which 464 (18.5%) samples were found to be positive for dengue viral infection. A majority of the cases were males [268 (57%)] when compared with females [196 (42%)]. Fever was the most common clinical presentation seen in all the patients, followed by headache (78.4%), myalgia (61%), body pain (49.3%), vomiting (40%), joint pain (31.5%), dry cough (19%), nausea (14%), abdominal pain (8%), diarrhea (5.6%), retro-orbital pain (04%), burning micturition (2.4%), and rashes (0.6%). Among atypical manifestations, hepatomegaly [32 (7%)] was the most common, followed by splenomegaly [23 (5%)], bradycardia [18 (4%)], meningitis [6 (1.2%)], hemoptysis [5 (1%)], acalculous cholecystitis [4 (0.8%)], and acute pancreatitis [2 (0.4%)]. The study of hematological parameters showed thrombocytopenia was present in 179 (38.5%) patients, followed by leukopenia [77 (17%)] and raised hematocrit [29 (6.2%)].
Conclusion:
During ongoing epidemics, the clinical profile and atypical manifestations in clinically suspected dengue patients should be investigated early so that severe forms can be treated promptly.
Keywords: Atypical manifestation, clinical profile, dengue fever, hematological parameters
Introduction
Dengue, a common mosquito-borne viral disease, occurs in tropical and subtropical countries especially South and Southeast Asia countries, the Caribbean, Central, and South America, and Africa. Dengue virus (DENV) infection is the most rapidly spreading disease in the world with a 30-fold increase in incidence in the past 50 years.[1] The first dengue fever in India was reported in 1956 from Vellore and the first dengue hemorrhagic fever occurred in Calcutta in 1963.[2] Dengue is caused by one of the four serotypes of DEVN (DENV-1–DENV-4) belonging to the family Flaviviridae.[3] All the four serotypes of the virus have been in circulation and documented in Tamil Nadu.[4] Dengue fever is an acute febrile illness with frontal headache, retro-ocular pain, muscle pain, joint pain, and rash, even though other signs and symptoms could also be present (such as lymphadenopathy, petechiale, nausea, hepatomegaly, and different types of hemorrhagic manifestations).[5] Atypical manifestations are rare and include encephalopathy, encephalitis, seizures, hepatocellular damage, acalculous cholecystitis, myocarditis, pericardial effusion, and severe gastrointestinal hemorrhage.[6,7] The clinical presentation in dengue depends on the virus strain, as well as the age and immune status of the host.[3] This study aims to elucidate the salient clinical feature and laboratory findings of serologically confirmed cases of dengue fever. The elucidation of clinical profile is very important for primary care, management, and thus crucial for saving life.
Aim of the Study
This study aims to study the clinical profile and atypical manifestations in patients with dengue fever.
Materials and Methods
This retrospective observational study was conducted during the period from July 2011 to December 2018 at Sri Muthukumaran Medical College, Hospital and Research Institute, Chennai, India. Informed consent was taken from each patient and the study was approved by Institutional Ethical Committee (obtained on 23.12.2016 (46/IECs)). Serum samples were collected from clinically suspected cases of dengue and were confirmed by NS1 antigen, IgM, and IgG antibody by ELISA (J. Mitra and Co. Pvt. Ltd.). A detailed history was taken and careful clinical examination was performed on all the positive cases. Hematological parameters such as platelet count, hemoglobin, hematocrit (HCT) levels, complete blood count (CBC), and white blood cell count (WBC) were also recorded.
Observation
During the study period, a total of 2502 patients were suspected to have dengue fever, out of which 464 (18.5%) samples were found to be positive. In our study population, the highest numbers of dengue-positive cases were screened in the year 2017 (74.8%), followed by 2013 (27.7%) and 2016 (18.8%) as shown in [Table 1]. A majority of the cases were males 268 (57.7%) and females were 196 (42.2%). About 45% of positive cases belonged to adult age groups (18–44 years) followed by younger age group <18 years (30%) [Table 2]. Fever was the most common clinical presentation which was found among all the patients, followed by headache (78.4%), myalgia (61.2%), body pain (49.3%), vomiting (40%), joint pain (31%), dry cough (19%), nausea (13.5%), abdominal pain (8%), diarrhea (5.6%), retro-orbital pain (4%), burning micturition (2.5%), and rashes (0.6%) [Table 3]. In this study, 90 (19.3%) patients had atypical manifestations. Hepatomegaly [32 (7%)] was the most common manifestation, followed by splenomegaly [23 (5%)], bradycardia [18 (4%)], meningitis [6 (1.2%)], hemoptysis [5 (1%)], acalculous cholecystitis [4 (0.8%)], and acute pancreatitis [2 (0.4%)] [Table 4]. The majority of the patients were positive for NS1 Ag 290 (62.5%) followed by IgG 80 (17.2%), IgM 53 (11.4%), and IgM + IgG 41 (9%) as shown in [Table 5]. Raised HCT was found in 29 (6.2%) and leukopenia (<4000/mm3) was found in 77 (16.5%) patients. Thrombocytopenia was observed in 179 (38.5%) cases [Table 6].
Table 1.
Year-wise distribution of dengue cases during the study period
| Year | Total no. of cases | Positive cases |
|---|---|---|
| 2011 | 346 | 9 (2.6%) |
| 2012 | 463 | 25 (5.3%) |
| 2013 | 457 | 127 (27.7%) |
| 2014 | 342 | 72 (21%) |
| 2015 | 460 | 85 (18.4%) |
| 2016 | 90 | 17 (18.8%) |
| 2017 | 151 | 113 (74.8%) |
| 2018 | 193 | 16 (8.2%) |
| Total | 2502 | 464 (18.5%) |
Table 2.
Age and sex-wise distribution of dengue cases (n=464)
| Age groups (years) | Males | Females | Total |
|---|---|---|---|
| <18 | 81 | 57 | 138 (30%) |
| 18-44 | 118 | 89 | 207 (45%) |
| 45-60 | 47 | 35 | 82 (18%) |
| >60 | 22 | 15 | 37 (8%) |
| Total | 268 (57.7%) | 196 (42.2%) |
Table 3.
Clinical features of dengue-positive cases (n=464)
| Clinical features | No. of cases (%) |
|---|---|
| Fever | 439 (95%) |
| Headache | 364 (78.4%) |
| Myalgia | 284 (61.2%) |
| Body pain | 229 (49.3%) |
| Vomiting | 186 (40%) |
| Joint pain | 144 (31%) |
| Dry cough | 89 (19.1%) |
| Nausea | 63 (13.5%) |
| Abdominal pain | 38 (8.1%) |
| Diarrhea | 26 (5.6%) |
| Retro-orbital pain | 19 (4%) |
| Burning micturition | 12 (2.5%) |
| Rashes | 03 (0.6%) |
Table 4.
Atypical clinical manifestations in dengue patients (n=90)
| Clinical features | No. of cases (%) |
|---|---|
| Hepatomegaly | 32 (7%) |
| Splenomegaly | 23 (5%) |
| Bradycardia | 18 (4%) |
| Meningitis | 6 (1.2%) |
| Hemoptysis | 05 (1%) |
| Acalculous cholecystitis | 04 (0.8%) |
| Acute pancreatitis | 2 (0.4%) |
| Total | 90 (19.3%) |
Table 5.
Serological marker distribution of dengue cases
| Total no. of patients (n=464) | Dengue-specific marker | |||
|---|---|---|---|---|
| NS1 Ag | IgM | IgG | IgG + IgM | |
| Dengue-positive cases | 290 (62.5%) | 53 (11.4%) | 80 (17.2%) | 41 (9%) |
Table 6.
Hematological parameters of dengue-positive cases (n=464)
| Investigation | No. of cases (%) |
|---|---|
| Thrombocytopenia (<150,000/mm3) | 179 (38.5%) |
| Leucopenia (<4000/mm3) | 77 (16.5%) |
| Raised hematocrit | 29 (6.2%) |
Discussion
Dengue is emerging as a major health problem and regular outbreaks of dengue infection have been occurring throughout India.[8,9] The provision of adequate care to patients with suspected dengue in primary care settings requires effective clinical evaluation, laboratory testing, and qualified professionals who know how to recognize warning signs and give appropriate guidance to prevent expended dengue.[10] Rapid urbanization, globalization, increasing population, poor solid waste, and water management have given rise to new habitats for mosquito breeding thereby increasing the number of cases and deaths.[1,11] The identification of dengue cases is possible by distinct clinical features. Studies describe that atypical manifestations in dengue fever are multisystemic and multifaceted with organ involvement, such as liver, brain, heart, kidney, and central nervous system.[12] In this study, we investigated the different clinical profile and atypical manifestations.
Incidences of dengue positivity were increasing for the past few years. In our study, we found that the highest number of dengue-positive cases was reported in the year 2017 (74.8%), 2013 (27.7%), and 2016 (18.8%), which were similar to that of previous studies reported.[13,14] Studies revealed that the majority of the cases were in the age group of 15–44 years, followed by other groups. In this study, males [268 (57.7%)] were predominant than females [196 (42.2%)]. These findings well correlate with previous studies.[15] Fever was the most common clinical presentation which was found among all the presenting patients (100%). Headache (78%) and myalgia (61%) were seen in the majority of cases, followed by joint pain (31%), dry cough (19%), abdominal pain (8%), diarrhea (5.6%), vomiting (32%), and nausea (14%) which is concordant with the study by Hasan SR et al.[16]
Atypical symptoms have been observed in this study, which is low compared with previous study done by Nagarajan N et al.[17] Retro-orbital pain as a cardinal feature of dengue fever was seen in few (4%), of our patients, while Denys EF et al. had reported 16.1%.[18] Burning micturition (8%), hemoptysis (2%), and rashes (0.2%) were not frequent in our study when compared with other studies.[19] Hepatomegaly is highly specific for the development of both dengue hemorrhagic fever and dengue shock syndrome. In our study, 31 (7%) patients had hepatomegaly which correlates with a previous study done by Row EK et al.[20] In our study, splenomegaly was 5% which is concordant with a previous study reported by Anurag Prasad et al.[21] Other less common atypical manifestations were bradycardia [18 (4%)], meningitis [6 (1.2%)], hemoptysis [5 (1%)], acalculous cholecystitis [4 (0.8%)], and acute [pancreatitis 2 (0.4%)]. This differs from other studies where bradycardia, meningitis, hemoptysis, and acalculous cholecystitis were detected in higher percentage of confirmed dengue fever.[22,23,24,25]
Out of 2038 samples of clinically suspected dengue cases, 464 (23%) were found to be positive by ELISA. The majority of the samples were found positive for NS1 antigen 290 (63%), which indicates high sensitivity of the test for early diagnosis of disease, followed by IgG and IgM antibodies, which is similar to a study conducted by Anand et al.[26] In our study, thrombocytopenia was present in 179 (39%) patients <150,000/mm3, which is slightly less than the study conducted by Ahmed NH et al. Recent studies have established HCT > 40% as a prognostic factor for severe dengue.[26,27,28,29] In our study, we have found raised HCT in 29 (6.2%) patients. Low leucocyte count may be due to virus-induced inhibition of myeloid progenitor cells or due to destruction.[30] We found that 11% had leucocyte count <5000, almost similar to a study by Chaloemwong J et al.[31] An understanding of the course of disease progression, risk factors, recognition of the warning signs, and look out for clinical problems during the different phases of the disease will enable primary care physicians to manage dengue fever in an appropriate and timely manner to reduce morbidity and mortality.[32] Primary care physician should impart health education about dengue fever to the rural community regularly, through health camps or interpersonal communication based on health awareness programs.[33] Thus, atypical presentations should prompt us to investigate for dengue especially during ongoing epidemics so that primary care and management is very important in preventing expanded dengue syndrome.
Conclusion
To conclude, the clinical profile of the dengue fever cases is changing in different epidemics, even in the same regions and with the period of time. Primary care physician should have a high index of suspicion to detect and timely manage the atypical manifestations of dengue fever as they are no more a rare entity and will continue to rise so long as they are looked for carefully in dengue patients. This study thus indicates the need for a continuous seroepidemiological surveillance for the early and definite identification of the clinical features and atypical manifestations of dengue infection.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgement
The authors sincerely thank the physicians, staff nurse, and technicians of Sri Muthukumaran Medical College Hospital and Research Institute, Chennai, India, for providing their help in identifying the patient, collection of clinical data, and obtaining serum samples.
References
- 1.Damodar T, Dias M, Mani R, Shilpa KA, Anand AM, Ravi V, et al. Clinical and laboratory profile of dengue viral infections in and around Mangalore, India. Indian J Med Microbiol. 2017;35:256–61. doi: 10.4103/ijmm.IJMM_15_423. [DOI] [PubMed] [Google Scholar]
- 2.Gupta N, Srivastava S, Jain A, Chaturvedi UC. Dengue in India. Indian J Med Res. 2012;136:373–90. [PMC free article] [PubMed] [Google Scholar]
- 3.Bäck AT, Lundkvist A. Dengue viruses-An overview. Infect Ecol Epidemiol. 2013;30:3. doi: 10.3402/iee.v3i0.19839. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Ahmed MM. Clinical profile of dengue fever infection in King Abdul Aziz University Hospital Saudi Arabia. J Infect Dev Ctries. 2010;8:503–10. doi: 10.3855/jidc.1038. [DOI] [PubMed] [Google Scholar]
- 5.Low SL, Lam S, Wong WY, Teo D, Ng LC, Tan LK. Dengue seroprevalence of healthy adults in Singapore: Serosurvey among blood donors, 2009. Am J Trop Med Hyg. 2015;93:40–5. doi: 10.4269/ajtmh.14-0671. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Goh BK, Tan SG. Case of dengue virus infection presenting with acute acalculous cholecystitis. J Gastroenterol Hepatol. 2006;21:923–4. doi: 10.1111/j.1440-1746.2006.04122.x. [DOI] [PubMed] [Google Scholar]
- 7.Ahmed S, Ali N, Tariq WU. Neurological manifestations as presenting feature in dengue Fever. J Coll Physicians Surg Pak. 2007;17:236–7. [PubMed] [Google Scholar]
- 8.Nadkar MY, Khot W. Dengue in India: Matters of the Heart. J Assoc Physicians India. 2019;67:11–2. [PubMed] [Google Scholar]
- 9.Mutheneni SR, Morse AP, Caminade C, Upadhyayula SM. Dengue burden in India: Recent trends and importance of climatic parameters. Emerg Microbes Infect. 2017;6:e70. doi: 10.1038/emi.2017.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Freitas DA, Souza-Santos R, Wakimoto MD. Access to health care facilities of suspected dengue patients in Rio de Janeiro, Brazil. Cien Saude Colet. 2019;24:1507–1516. doi: 10.1590/1413-81232018244.11252017. [DOI] [PubMed] [Google Scholar]
- 11.Agarwal R, Kapoor S, Nagar R, Misra A, Tandon R, Mathur A, et al. A clinical study of the patients with dengue hemorrhagic fever during the epidemic of 1996 at Lucknow, India. Southeast Asian J Trop Med Public Health. 1999;30:735–40. [PubMed] [Google Scholar]
- 12.Kadam DB, Salvi S, Chandanwale A. Expanded dengue. J Assoc Physicians India. 2016;64:59–63. [PubMed] [Google Scholar]
- 13.Ganeshkumar P, Murhekar M, Poornima V, Saravana Kumar V, Sukumaran K, Anandaselvasankar A, et al. Dengue infection in India: A systematic review and meta-analysis. PLoS Negl Trop Dis. 2018;12:e0006618. doi: 10.1371/journal.pntd.0006618. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Mistry M, Goswami Y, Chudasama RK, Thakkar D. Epidemiological and demographic characteristics of dengue disease at a tertiary care centre in Saurashtra region during the year 2013. J Vector Borne Dis. 2015;52:299–303. [PubMed] [Google Scholar]
- 15.Chandralekha, Gupta P, Trikha A. The north Indian dengue outbreak 2006: A retrospective analysis of intensive care unit admissions in a tertiary care hospital. Trans R Soc Trop Med Hyg. 2008;102:143–7. doi: 10.1016/j.trstmh.2007.11.002. [DOI] [PubMed] [Google Scholar]
- 16.Hasan SR, Riaz M, Jafri FA. Characteristics and outcome of dengue infection; clinical perspective from a secondary care hospital of Karachi. Pak J Med Sci. 2013;29:115–8. doi: 10.12669/pjms.291.2742. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Natarajan N, Cugati S, Padi TR, Padmapriya N. Patterns and trends in atypical manifestations of dengue among inpatient adults in tertiary care teaching institute of South India. Int J Contemporary Med Res. 2017;4:2152–6. [Google Scholar]
- 18.Fujimoto DE, Koifman S. Clinical and laboratory characteristics of patients with dengue hemorrhagic fever manifestations and their transfusion profile. Rev Bras Hematol Hemoter. 2014;36:115–20. doi: 10.5581/1516-8484.20140027. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Thomas EA, John M, Kanish B. Mucocutaneous manifestations of Dengue fever. Indian J Dermatol. 2010;55:79–85. doi: 10.4103/0019-5154.60359. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Rowe EK, Leo YS, Wong JG, Thein TL, Gan VC, Lee LK. Challenges in dengue fever in the elderly: Atypical presentation and risk of severe dengue and hospital-acquired infection. PLoS Negl Trop Dis. 2014;8:e2777. doi: 10.1371/journal.pntd.0002777. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Prasad A, Yasmeen M, Prasad GS. Study of acute acalculuos cholecystitis as an atypical manifestation in dengue fever. Int J Med Sci Public Health. 2015;4:1231–4. [Google Scholar]
- 22.Lateef A, Fisher DA, Tambyah PA. Dengue and relative bradycardia. Emerg Infect Dis. 2007;13:650–1. doi: 10.3201/eid1304.061212. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Goswami RP, Mukherjee A, Biswas T, Karmakar PS, Ghosh A. Two cases of dengue meningitis: A rare first presentation. J Infect Dev Ctries. 2012;6:208–11. doi: 10.3855/jidc.2241. [DOI] [PubMed] [Google Scholar]
- 24.Mohamed NA, Raoofb EA, Ibraheem HA. Respiratory manifestations of dengue fever in Taiz-Yemen. Egyp J Chest Dis Tuberculosis. 2013;62:319–23. [Google Scholar]
- 25.Chandey M, Kaur H, Kaur S. Acute acalculous cholecystitis in dengue fever patients. Int J Adv Med. 2017;4:375–7. [Google Scholar]
- 26.Anand AM, Sistla S, Dhodapkar R, Hamide A, Biswal N, Srinivasan B. Evaluation of NS1 antigen detection for early diagnosis of dengue in tertiary hospital in Southern India. J Clin Diagn Res. 2016;10:DC01–4. doi: 10.7860/JCDR/2016/15758.7562. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Ahmed NH, Broor S. Dengue fever outbreak in Delhi, North India: A clinico-epidemiological study. Indian J Community Med. 2015;40:135–8. doi: 10.4103/0970-0218.153884. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Halstead SB. Controversies in dengue pathogenesis. Paediatr Int Child Health. 2012;32:5–9. doi: 10.1179/2046904712Z.00000000045. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Agrawal VK, Prusty BSK, Reddy CS, Mohan Reddy GK, Agrawal RK, Sekher Srinivasarao Bandaru VC. Clinical profile and predictors of Severe Dengue disease: A study from South India. Caspian J Intern Med. 2018;9:334–340. doi: 10.22088/cjim.9.4.334. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Laul A, Laul P, Merugumala V, Pathak R, Miglani U, Saxena P. Clinical profiles of dengue infection during an outbreak in Northern India. J Trop Med. 2016;2016:5917934. doi: 10.1155/2016/5917934. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Chaloemwong J, Tantiworawit A, Rattanathammethee T, Hantrakool S, Chai-Adisaksopha C, Rattarittamrong E, et al. Useful clinical features and hematological parameters for the diagnosis of dengue infection in patients with acute febrile illness: A retrospective study. BMC Hematol. 2018;18:20. doi: 10.1186/s12878-018-0116-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Lum L, Ng CJ, Khoo EM. Managing dengue fever in primary care: A practical approach. Malays Fam Physician. 2014;9:2–10. [PMC free article] [PubMed] [Google Scholar]
- 33.Verma R, Bhalla K, Dhankar M, Kumar R, Dhaka R, Agrawal G. Practices and knowledge regarding dengue infection among the rural community of Haryana. J Family Med Prim Care. 2019;8:1752–4. doi: 10.4103/jfmpc.jfmpc_6_19. [DOI] [PMC free article] [PubMed] [Google Scholar]