Introduction
Dengue fever, caused by the dengue virus of the Flaviviridae family, is transmitted to humans through the bite of Aedes mosquitoes and is associated with substantial morbidity and mortality worldwide.Reference Simmons, Farrar, Nguyen and Wills1–Reference Kakkar3 The four distinct serotypes of the dengue virus (DENV-1 to DENV-4) can lead to either asymptomatic seroconversion or symptomatic disease. Owing to their antigenic diversity, cross-protective immunity is short-lived, predisposing individuals to multiple sequential infections.Reference Simmons, Farrar, Nguyen and Wills1
Dengue fever is a systemic and dynamic illness, presenting a wide range of clinical manifestations, from non-severe to severe forms.Reference Simmons, Farrar, Nguyen and Wills1 The illness begins abruptly after an incubation period of 3–7 days and progresses through three distinct phases in patients with moderate to severe disease: febrile, critical and recovery. The severity of the illness typically becomes apparent around the time of defervescence—the transition from the febrile to the afebrile phase—which often coincides with the onset of the critical phase due to the dynamic nature of the disease. Dengue fever remains endemic in India, with a shifting epidemiological trend from predominantly urban prevalence to increasing incidence in peri-urban and rural regions.Reference Chakravarti, Arora and Luxemburger4, Reference Figueiredo, Mourão, Abi-Abib, Oliveira, Roque and Azara5
Dengue hemorrhagic fever often begins with symptoms indistinguishable from classical dengue; however, clinical deterioration typically occurs by the third to fourth day of illness. During this critical phase, patients may develop agitation, lethargy, tachycardia, hypotension, spontaneous bleeding, cyanosis and hypothermia.Reference Simmons, Farrar, Nguyen and Wills1, 2, Reference Guzmán and Kourí6 Laboratory confirmation of dengue infection is most commonly performed by detecting non-structural protein 1 (NS1) antigen through an enzyme-linked immunosorbent assay (ELISA).Reference Zanluca, Melo, Mosimann, Santos, Santos and Luz7, Reference da Fonseca and Fonseca8
Common ENT manifestations in dengue fever include rhinitis, sore throat, nasal obstruction, otalgia, dizziness and bleeding symptoms such as epistaxis and gingival bleeding, along with salivary gland alterations.Reference Guzmán and Kourí6
Hearing loss following viral infections is often sensorineural, though it may also be mixed (as seen with measles or cytomegalovirus [CMV]) or conductive. Proposed mechanisms for sensorineural hearing loss include direct viral damage or immune-mediated injury to the peripheral auditory system (as seen with CMV). The virus may affect microvascular permeability and thromboregulatory mechanisms, possibly due to disruption of the endothelial glycocalyx layer.Reference Cohen, Durstenfeld and Roehm9–Reference Casetta, Ciorba, Cesnik, Trevisi, Tugnoli and Bovo12
There is a dearth of literature establishing a definitive association between dengue and sensorineural hearing loss. However, literature suggested a possible link between the two.Reference Soni, Bohra, Nair, Kaushal, Patro and Goyal10 This study aims to further explore the potential association between dengue fever and hearing loss.
Materials and methods
A case–control study was conducted, in which 40 patients diagnosed with dengue fever were included as cases, and 39 patients with other febrile illnesses not known to cause hearing loss were included as controls. Patients presented to the Department of General Medicine of our hospital between September 2022 and September 2024 with fever were further worked up. NS1 antigen-positive dengue fever patients treated on in-patient or out-patient basis were enrolled in the study as cases and other patients with pyrexia presented to ENT or General Medicine out-patient department were taken as controls.
Patients aged 18 to 65 years were included in the study. Patients who had a prior history of chronic otitis media or hearing loss, hypothyroidism, diabetes mellitus and neurological diseases were excluded from the study. We also excluded patients with a history of exposure to loud noise and ototoxic drugs.
Ethical clearance was obtained from the Institutional Ethics Committee prior to the commencement of the study.
Methods
A brief history, along with clinical examination, including otoscopy and tuning fork test were done as soon as the patients were diagnosed with febrile illness. Baseline evaluation of fever was done, including complete hemogram, serology workup for febrile illnesses including dengue (NS1 antigen), malaria (peripheral smear for malaria parasite and malaria antigen rapid), chikungunya (immunoglobulin [Ig] M ELISA and IgG ELISA), typhoid (IgM ELISA & IgG ELISA), scrub typhus (IgM ELISA & RTPCR) etc. Hearing evaluation was done as soon as the patients were fit to undergo the test, using pure tone audiometry (PTA) and tympanometry. Using PTA, both air conduction (AC) and bone conduction (BC) thresholds were measured at different frequencies (250 Hz, 500 Hz, 1000 Hz, 2000 Hz, 4000 Hz and 8000 Hz). For each ear, the pure tone average was calculated as the mean of the thresholds measured at 500 Hz, 1000 Hz and 2000 Hz, representing the speech frequencies. Tympanometry was done to assess the status of the middle ear as it is an objective measure of the tympano-ossicular system function.Reference Alvarenga, Melo, Rays, Amorim, Jacob and Araújo13
Results and analysis
Statistical analysis
The data were entered in Microsoft excel and analysed using SPSSv26 (IBM Corp. released 2021 IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY). Descriptive analysis was done, tests for normality were applied. Quantitative variables were analysed using the t-test, analysis of variance (ANOVA) test and non-parametric data were analysed using Mann–Whitney U test. A p-value of less than 0.05 was considered as significant.
Results
A total of 79 patients were included in the study and assessed prospectively following confirmation of dengue infection with NS1 antigen positivity. All participants underwent detailed clinical evaluation and audiological testing.
Demographic characteristics
Among the 79 participants, 40 were dengue-positive (cases) and 39 were dengue-negative (controls). The demographic distribution is summarised in Table 1. The majority of patients in both groups were females. The mean age among cases was 26.92 plus or minus 8.35years, while that among controls was 24.87 plus or minus 12.9 years.
Demographic characteristics of study participants
Audiological findings
PTA revealed a higher incidence of hearing loss among dengue-positive patients compared to controls. The association between dengue infection and hearing loss was statistically significant (χ2 = 13.8; df = 1; p < 0.001). The odds ratio for developing hearing loss in dengue-positive patients was 34.6 (95 per cent confidence interval [CI]: 1.97–610), indicating a strong association (Table 2). Though the pre-illness hearing levels were not available, exclusion criteria were framed in such a way that only patients without any evidence of pre-existing hearing loss were included in the study.
Association between dengue infection and hearing loss
Comparison of hearing thresholds
On comparison of air and bone conduction thresholds between the two groups, dengue-positive patients demonstrated significantly elevated thresholds in both ears, consistent with mild sensorineural hearing loss. ANOVA revealed a statistically significant difference (p < 0.001) for all parameters (Table 3).
Comparison of mean hearing thresholds between dengue-positive and control groups
dB = decibel; HL = hearing loss; SD = standard deviation.
Among the patients diagnosed with dengue fever, platelet counts and C-reactive protein (CRP) levels were additionally evaluated to explore their potential association with hearing loss, based on preliminary findings from the author’s pilot study suggesting a possible correlation.Reference Soni, Bohra, Nair, Kaushal, Patro and Goyal10
Platelet count analysis
Among dengue-positive patients, the mean platelet count was 58,000/mm3 (range: 6,000–115,000). The distribution was non-normal (Shapiro–Wilk W = 0.907, p = 0.003). Using the Mann–Whitney U test, a strong, statistically significant difference was observed in platelet counts between patients with and without hearing loss (U = 0.00; p < 0.001) (Table 4).
Platelet count distribution among dengue-positive patients
CRP levels
The mean CRP level among dengue-positive patients was 36.2 mg/l (range: 2–170). Elevated CRP levels were observed in patients with hearing loss compared to those without. Data distribution was non-normal (Shapiro–Wilk W = 0.749; p < 0.001). The Mann–Whitney U test demonstrated a statistically significant difference between the two groups (U = 1.00; p < 0.001) (Table 5).
C-reactive protein (CRP) distribution among dengue-positive patients
Discussion
The present study highlights a previously underreported clinical finding—sensorineural hearing loss (SNHL) following dengue fever. Although ENT manifestations such as otalgia, nasal bleeding and dizziness are well-documented in dengue, the presence of SNHL as a potential sequela is novel and clinically significant.
Among the 79 participants evaluated, 15.2 per cent of dengue-positive patients exhibited hearing loss, while none of the control subjects were affected. The odds ratio of 34.6 (95 per cent CI: 1.97–610) underscores a strong correlation between dengue infection and auditory dysfunction. The findings highlight an under-recognised neuro-otological manifestation of dengue fever.
The pathophysiological basis of hearing loss in viral illnesses is multifactorial. Infections such as mumps, measles, CMV and, more recently, Zika and West Nile viruses—both members of the Flaviviridae family like dengue—are known to affect the cochlear and vestibular systems. The proposed mechanisms include direct viral invasion of the cochlea and cochlear nerve, reactivation of latent viral infection and immune-mediated damage. In dengue, vascular endothelial damage due to cytokine storm and immune complex deposition is a well-known phenomenon. The cochlea is a highly vascular structure with end-arterial supply, making it particularly vulnerable to ischemic or inflammatory insults. The mild negative correlation between hearing loss and platelet count in our study supports the hypothesis that microvascular injury, associated with thrombocytopenia, may contribute to cochlear damage.Reference Casetta, Ciorba, Cesnik, Trevisi, Tugnoli and Bovo12, Reference Weatherhead, Miller, Garcia, Hasbun, Salazar and Dimachkie14–Reference Vinhaes, Santos, Dias, Andrade, Bezerra and de Carwvalho16
Previous literature on hearing loss in flavivirus infections provides some corroborative context. Vinhaes et al. (2017) reported transient hearing loss in Zika virus infection, while Casetta et al. (2011) described bilateral SNHL in West Nile virus neuroinvasive disease.Reference Casetta, Ciorba, Cesnik, Trevisi, Tugnoli and Bovo12, Reference Vinhaes, Santos, Dias, Andrade, Bezerra and de Carwvalho16
Ribeiro et al. (2015) described a case of hemorrhagic dengue associated with SNHL. These sporadic reports highlight the plausibility of viral-induced auditory dysfunction across flaviviral infections, though large-scale studies remain lacking.Reference Ribeiro, Guimarães, Yazawa, Takara, de Carvalho and Zappelini15
Soni et al. reported reversible hearing loss in a case report of scrub typhus. The study mentioned that the rickettsieae directly invade the central nervous system and induce vasculitis in the acute stage and damage the cochlear division of the eighth cranial nerve.Reference Soni, Chhabra, Yadav and Gulia17
In the current study, both AC and BC thresholds were significantly elevated among dengue-positive patients in comparison with controls, indicating a sensorineural pattern of hearing loss. This finding suggests a cochlear or retrocochlear pathology, possibly secondary to viral invasion, immune complex deposition or microvascular compromise of the stria vascularis.
Our study identified a strong, statistically significant relationship between low platelet counts and hearing loss. Dengue-associated thrombocytopenia may cause microvascular occlusion and hemorrhagic changes in the inner ear, leading to cochlear hypoperfusion. Similar microangiopathic mechanisms have been implicated in viral-induced auditory dysfunctions, including CMV and mumps infections.Reference Cohen, Durstenfeld and Roehm9 The finding aligns with the hypothesis that vascular instability and endothelial injury in dengue may extend beyond systemic manifestations to involve inner ear microcirculation.Reference Srikiatkhachorn and Kelley11
Moreover, patients with hearing loss exhibited significantly elevated CRP levels, suggesting the role of systemic inflammation in auditory pathology. CRP is an acute-phase reactant reflecting cytokine activity, and elevated CRP correlates with vascular permeability and oxidative stress.Reference Simmons, Farrar, Nguyen and Wills1 The inflammatory milieu may compromise the blood–labyrinth barrier, allowing inflammatory mediators to access cochlear fluids, thereby altering ionic homeostasis and triggering outer hair cell dysfunction. This observation is consistent with literature implicating inflammatory pathways in virus-associated SNHL.Reference Cohen, Durstenfeld and Roehm9, Reference Soni, Bohra, Nair, Kaushal, Patro and Goyal10
It is noteworthy that ENT symptoms are often overlooked during dengue management due to the predominance of systemic and hemorrhagic manifestations. However, our findings suggest that auditory complaints should not be dismissed, especially in the early febrile or defervescence phases. The onset of hearing loss during the viremic phase or shortly after may indicate a direct or early immunological mechanism. Future studies incorporating temporal audiological monitoring could help delineate whether the hearing loss is acute, delayed or progressive.
Our study’s strength lies in its prospective design and control matching. Nevertheless, certain limitations must be acknowledged. First, the sample size was modest, and only three of the 12 dengue patients developed hearing loss could be followed-up, who had confirmed persistent hearing loss at follow-up, limiting the generalisability. Second, high-resolution MRI was not utilised to correlate the extent of neural involvement. Third, although we excluded patients with known co-morbidities or ototoxic exposure, subtle sub-clinical predispositions (e.g., early presbycusis or genetic vulnerability) cannot be entirely ruled out.
Another consideration is the potential for hearing loss due to high fever, dehydration or transient middle ear dysfunction secondary to systemic illness. However, tympanometric data did not suggest middle ear pathology in our patients, reinforcing the likelihood of sensorineural etiology.
Clinically, this study highlights the importance of considering dengue fever as a differential diagnosis in patients presenting with sudden or progressive hearing loss in endemic regions.
However, patients presenting with dengue febrile illness should undergo an audiological evaluation during their initial visit to obtain a baseline assessment. Early audiological testing and referral to ENT specialists during illness may be warranted for early detection of hearing loss in such cases.
• Viral infections such as mumps, measles, cytomegalovirus (CMV) and Zika can cause sensorineural hearing loss
• Dengue virus affects vascular permeability and can cause endothelial injury
• Only isolated case reports have suggested hearing loss after dengue
• Provides prospective evidence linking dengue infection to hearing loss
• Identifies thrombocytopenia and elevated C-reactive protein (CRP) as correlates of auditory dysfunction
• Suggests the need for early audiological evaluation in dengue patients for timely detection and management
Conclusion
Dengue infection is significantly associated with SNHL. Patients with lower platelet counts and higher CRP levels were more likely to develop auditory impairment, suggesting the role of inflammation and microvascular injury in cochlear dysfunction. Routine hearing evaluation should be considered in dengue patients to enable early detection and timely management. Further studies are needed to determine the reversibility and long-term impact of dengue-related hearing loss.
Acknowledgements
The authors thank all the audiology and laboratory staffs for their support.
Funding
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests
All authors declare that they have no conflict of interest.
Ethical standards
The authors assert that all procedures contributing to this work comply with the ethical standards of the national and institutional guidelines on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.
