A Promising Therapeutic Approach for Post-Lassa Fever Sensorineural Hearing Loss: A Case Report

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Saka This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7697165/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Lassa fever is a viral haemorrhagic illness endemic in West Africa, with Nigeria accounting for a significant proportion of global cases. While most patients recover, sensorineural hearing loss (SNHL) is a serious and often overlooked post-infectious complication. We present the case of a 13-year-old girl who developed sudden profound right-sided SNHL shortly after recovering from Lassa fever, despite a high cycle threshold (Ct) value on PCR, indicating low viral load. She was treated with intravenous mannitol and hydrocortisone, along with oral betahistine and neurovite, and demonstrated notable improvement in hearing over a one-month period. Follow-up revealed subclinical involvement of the contralateral ear, emphasizing the risk of bilateral progression. This case underscores that significant auditory sequelae can occur even at low viral loads and highlights the potential benefits of early pharmacologic intervention. It also reinforces the urgent need for routine hearing assessment and auditory rehabilitation in Lassa fever survivors. Virology Infectious Diseases Lassa Fever Hearing Loss Sensorineural Audiometry Pure-Tone Viral Hemorrhagic Fevers Post-Infectious Complications Mannitol Hydrocortisone Betahistine Figures Figure 1 Figure 2 Figure 3 Introduction Lassa fever is an acute viral haemorrhagic illness caused by the Lassa virus, endemic in West Africa and affecting tens of thousands of individuals annually, with Nigeria bearing a substantial share of the burden [ 1 ]. The Africa Centres for Disease Control and Prevention estimates that 100,000 to 300,000 Lassa fever infections occur each year, resulting in over 5,000 deaths, mostly in Nigeria, Sierra Leone, Guinea, Benin, Ghana, Mali, and Liberia. Notably, Nigeria alone accounts for approximately 75% of global Lassa fever cases annually [ 2 ]. In 2024, the Nigeria Centre for Disease Control (NCDC) reported 1,309 confirmed cases and 214 deaths, with Edo State accounting for nearly 30% of the confirmed cases nationwide [ 3 , 4 ]. Although many patients recover with appropriate care, a subset of survivors experience long-term complications, among which sensorineural hearing loss (SNHL) is particularly debilitating. Studies have shown that SNHL affects approximately 13–33% of Lassa fever survivors [ 5 – 12 ]. Despite progress in acute management, the post-recovery burden of Lassa fever, especially hearing impairment remains poorly characterized and under-addressed. SNHL can severely affect communication, educational attainment, occupational productivity, social engagement, and mental well-being [ 13 ]. The impact is especially profound in resource-limited settings like Edo State, where access to audiological services and rehabilitative care is scarce. In such contexts, children with hearing impairment risk academic under-performance, while adults face economic hardship and social isolation, further entrenching poverty. Globally, disabling hearing loss affects over 430 million people, a figure projected to nearly double by 2050, according to the World Health Organization. Therefore, integrating hearing loss surveillance into Lassa fever control programs is essential for holistic survivor management and strengthening health systems in endemic regions [ 14 ]. This case report underscores the potential role of pharmacologic intervention in managing post-Lassa fever sensorineural hearing loss (SNHL), a commonly overlooked complication with significant public health implications. Survivors of Lassa fever remain vulnerable to preventable disabilities that diminish quality of life and compound the socioeconomic burden in low-resource settings. Understanding and addressing such sequelae is essential for equitable infectious disease management. To date, no pharmacological intervention has been shown to reverse or improve Lassa-induced SNHL. Previous reports consistently describe poor outcomes, with most patients experiencing permanent hearing loss [ 12 , 15 – 17 ]. For example, one study observed no recovery in acute severe SNHL cases treated after the active phase of Lassa fever [ 12 ]. In contrast, our patient demonstrated significant functional recovery following early initiation of mannitol, hydrocortisone, betahistine, and neurovite, suggesting that timely combination therapy may alter prognosis. This distinction underscores the uniqueness of our case and its potential contribution to advancing therapeutic strategies for post-Lassa SNHL. Case presentation A 13-year-old girl who was managed for Lassa fever disease for 2 weeks, confirmed by polymerase chain reaction (PCR) test and was discharged home after the Lassa PCR result showed Negative. Two days post discharge, patient presented with a febrile illness and was admitted in Children Emergency (CHER) Ward, managed for Malaria to rule out Lassa fever, however, repeated Lassa PCR was not significant (high cycle threshold values) [ 18 ]. Since she was stable, the patient was discharged home. Two days post-discharge, patient developed sudden profound hearing loss of the right ear and presented to otolaryngology clinic four days after the onset of hearing loss. Patient was admitted and examined. Voice test conducted and patient didn't respond to whisper, conversation and loud voice while the left ear was closed by pressing on the tragus. Weber test was done and sound lateralized to the unaffected (left) ear. Otoscopic examination revealed normal findings in both ears. Pure tone audiometry (PTA) could not be done at presentation as service were not available. On admission, patient was placed on intravenous (IV) mannitol at 2g/kg over 30mins and then repeated after 8 hours, IV hydrocortisone 2mg/kg 8hourly, Tab betahistine 8mg 12hourly and Tab neurovite one tablet 12hrly. Sixteen (16) hours on admission, mother informed us that the patient could hear on the affected ear. She was further examined and patient responded to loud voice. Then PTA was done as reported in Fig. 1 , with a right pure tone average of 102dB and left pure tone average of 25dB (Fig. 1 ). Patient was discharged home on Tabs prednisolone, betahistine and neurovite. Three days following discharge, she complained of persistent tinnitus and peppery sensation in the affected right ear and increased sensitivity to normal everyday sounds, suggestive of hyperacusis, nerve irritation or acoustic trauma. Repeated PTA one-week post-discharge showed increased pure tone average in the left ear (47dB) and reduced pure tone average in the right ear (80dB) as show in Fig. 2 . One-month post-discharge pure tone average revealed 43dB in the left and 57dB in the right (Fig. 3 ) (Table 1 ). Table 1 Summary of pure tone average 16 hours on admission 1-week post-discharge 1-month post-discharge Pure Tone Average Right Ear Left Ear Right Ear Left Ear Right Ear Left Ear 102dB 25dB 80dB 47dB 57dB 43dB Discussion This case highlights important clinical and public health considerations regarding post-Lassa fever complications, particularly sensorineural hearing loss (SNHL). One of the key findings from this case is the development of profound right-sided hearing loss in a patient recently discharged after Lassa fever treatment, despite having a high cycle threshold (Ct) value on PCR, typically interpreted as low viral load [ 18 ]. This challenges the current practice of discharging patients solely based on viral load. Our findings suggest that a low level of circulating virus, as indicated by high Ct values, does not preclude the development of significant sequelae such as SNHL. Thus, discharging patients solely on account of low viral load should be discouraged until comprehensive post-recovery evaluations, including auditory screening, are conducted. Additionally, the sudden increase in the pure tone average (PTA) in the unaffected (left) ear from 25 to 47 dB raises concerns about subclinical or evolving bilateral auditory involvement, possibly due to ongoing viral or immune-mediated inner ear pathology. This indicates that Lassa virus activity or its sequelae may persist beyond the viraemic phase and may not be fully captured by PCR Ct values. Hence, early audiological intervention is necessary, and routine hearing assessments should be incorporated into the follow-up of all Lassa fever survivors, especially in endemic areas. The pathogenesis of sensorineural hearing loss in Lassa fever is not clear. However, it has been suggested in some studies that the hearing loss results from an exaggerated immune response against the inner ear structures [ 15 , 16 ]. In another study using the mouse model, damage to cochlear hair cell and degeneration of the spiral ganglion cells of the auditory nerve, thinning of the stria vascularis were observed. Distension of the Reisners membrane, infiltration of blood cells within the scala tympani and minor loss of inner and outer hair cells were also seen [ 19 ]. This case underscores the need for research to determine the level of Lassa viral load that becomes cytotoxic to cochlear and neural structures. While Ct values provide an estimate of viral burden, the precise threshold at which the virus initiates irreversible auditory damage remains undefined. Establishing this threshold would not only enhance our understanding of viral pathogenesis but also help refine discharge criteria and survivor monitoring protocols. The positive response to IV mannitol and hydrocortisone in this case suggests that endolymphatic hydrops and inflammation may play roles in the pathogenesis of Lassa-related SNHL. Mannitol, an osmotic diuretic, could help reduce intracochlear pressure, while hydrocortisone likely exerts anti-inflammatory effects that reduce neural injury. Additionally, betahistine, a histamine analogue, may improve inner ear blood flow through vasodilation, and neurovite (a vitamin B complex) may support nerve regeneration. These mechanisms align with existing approaches and empiric protocols to managing ototoxic and inflammatory hearing loss [ 20 ]. Although the exact pathophysiology of Lassa-induced hearing impairment remains unclear, previous studies have proposed four plausible mechanisms: direct viral invasion of the cochlea, immune-mediated cochleitis, cochlear ischemia, and vascular compromise, all of which are compatible with the clinical progression observed in this case [ 21 ]. Given the potential benefits observed with the combination of betahistine, prednisolone, and neurovite in patients with post-Lassa SNHL, we suggest that further research should explore the prophylactic use of these agents in all Lassa survivors at pre and post-discharge. This strategy could be especially valuable in settings where routine audiological screening is unavailable. While the routine inclusion of these agents in discharge medications may hold promise for preventing or mitigating delayed-onset hearing loss, this approach require validation through randomized controlled trials before formal adoption into treatment guidelines. Early intervention may prevent permanent damage; however, many patients present late, when neural injury has already become irreversible. Consequently, survivor follow-up must prioritize early screening, especially in rural and low-resource settings where auditory care is limited. Although the clinical presentation strongly suggests Lassa-induced SNHL, alternative causes must be considered. Malaria, for which the patient was briefly treated, can rarely cause hearing impairment, but her normal otoscopic findings and temporal association with recent Lassa infection make this less likely. Ototoxic drug exposure was excluded as the patient did not receive aminoglycosides or other known ototoxins during hospitalization. Idiopathic sudden SNHL remains a possibility; however, the onset immediately following confirmed Lassa fever, combined with the absence of other systemic causes, supports a Lassa-related aetiology. These considerations strengthen the causal inference while acknowledging diagnostic uncertainty inherent to single-case reports. Beyond this case, there are increasing anecdotal reports from otolaryngologists in endemic regions of sudden hearing loss following febrile illnesses, which remain a diagnostic challenge. While many of these cases may be unrecognized sequelae of Lassa fever, they are often not evaluated due to lack of confirmatory diagnostics and audiological infrastructure. These patterns suggest that the true burden of post-infectious hearing loss may be under-reported, and the link between febrile illnesses and SNHL in endemic areas remains a puzzle yet to be fully unravelled. Despite the growing recognition of these complications, auditory research in Lassa fever survivors is grossly underfunded. There is a compelling need for investment in rural hearing services, including routine audiometric screening, community-based rehabilitation programs, training of audiology personnel, and subsidization of hearing aids and cochlear implants. As many SNHL cases caused by Lassa virus are irreversible due to late presentation, affordable access to assistive devices like cochlear implants is critical, especially in low-resource settings. This report has several limitations. First, it represents a single case, limiting generalizability. Second, baseline audiometry prior to Lassa infection was not available, precluding absolute confirmation of new-onset hearing loss. Third, advanced imaging (e.g., MRI or CT) was not performed, which could have excluded structural or vascular causes of SNHL. Despite these limitations, the temporal relationship between Lassa fever recovery and onset of profound SNHL, coupled with treatment response, provides valuable clinical insights. Conclusion This case adds to the growing evidence that post-Lassa fever hearing loss is an urgent and under-addressed public health issue. A multi-pronged approach involving early diagnosis, pharmacologic research, auditory rehabilitation, and policy-driven investment is essential to reduce preventable disability among survivors and to improve long-term outcomes in Lassa-endemic regions. Declarations Authors’ contributions MA led patient management and contributed to the writing, editing and review of the final manuscript. FFB led patient management and contributed to the writing, editing and review of the final manuscript. SAS conceptualized, drafted the original manuscript, edited, reviewed the manuscript and managed patient under supervision of FFB and MA. MU conducted audiometry and contributed to writing and reviewing of final manuscript. EO, DA, JO, OJE, and EA contributed to the writing, editing and review of this manuscript. Ethics approval Our institution does not require ethical approval for reporting individual cases or case series. Informed consent Written informed consent for publication of her clinical details and/clinical images was obtained from the legal guardian. A copy of the consent form is available for review by the Editor of this journal. Availability of data and materials All the information about the patient is in the medical record with the clinicians (FFB and SAS) participating in this article. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors Acknowledgement This case report was prepared in accordance with CARE (CAse REport) guidelines to ensure transparency and completeness. The completed CARE checklist has been attached as a supplementary file References World Health Organisation (WHO). Lassa fever - Nigeria . World Health Organisation (WHO), https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON463 (2023, accessed 26 May 2026). Africa Centers for Disease Control and Prevention. Lassa fever . Africa CDC, https://africacdc.org/disease/lassa-fever/ (2018, accessed 26 May 2025). Nigeria Centre for Disease Control and Prevention (NCDC). Lassa Fever Situation Report . NCDC: NCDC, https://www.ncdc.gov.ng/themes/common/files/sitreps/a45a720bd6ddd1e75a5a3e7e6195e412.pdf (December 2024, accessed 27 April 2025). Reliefweb. Nigeria: Epidemic - 01-2024 - Lassa Fever Outbreak #3 (2024-03-28). Nigeria . Available from https://reliefweb.int/report/nigeria/nigeria-epidemic-01-2024-lassa-fever-outbreak-3-2024-03-28. Accessed March 3, 2025 Best KC, Ameh E, Weldon C, et al. Double stigma: a cross-sectional study of Lassa patients with hearing loss in North Central Nigeria. Front Public Health 2024; 12: 1395939. https://doi.org/10.3389/fpubh.2024.1395939 Chime EN, Chime PE, Nwosu JN. Hearing Loss in Lassa Fever: A Systematic Review. Open J Prev Med 2022; 12: 239–247. https://doi.org/10.4236/ojpm.2022.1211018 Ficenec SC, Percak J, Arguello S, et al. Lassa Fever Induced Hearing Loss: The Neglected Disability of Hemorrhagic Fever. Int J Infect Dis 2020; 100: 82–87. https://doi.org/10.1016/j.ijid.2020.08.021 Mateer EJ, Huang C, Shehu NY, et al. Lassa fever–induced sensorineural hearing loss: A neglected public health and social burden. PLoS Negl Trop Dis 2018; 12: e0006187. https://doi.org/10.1371/journal.pntd.0006187 Reed NS, Brewer CC, Akintunde G, et al. Report of a SPEAC webinar 22 september 2023: Sensorineural hearing loss, lassa virus disease and vaccines. Vaccine 2025; 43: 126525. https://doi.org/10.1016/j.vaccine.2024.126525 Saka SA. The Critical Role of Otolaryngologists in Managing Lassa Fever Sequelae: A Call for Action. J Otolaryngol - Head Neck Surg 2025; 54: 19160216251326559. https://doi.org/10.1177/19160216251326559 Saka SA, Lawal QO, Otaigbe O, et al. Lassa fever survivors: long-term health effects and chronic sequelae – a scoping review. BMC Infect Dis 2025; 25: 823. https://doi.org/10.1186/s12879-025-11262-1 Okokhere PO, Ibekwe TS, Akpede GO. Sensorineural hearing loss in Lassa fever: two case reports. J Med Case Reports 2009; 3: 36. https://doi.org/10.1186/1752-1947-3-36 Olusanya BO, Newton VE. Global burden of childhood hearing impairment and disease control priorities for developing countries. The Lancet 2007; 369: 1314–1317. World Health Organisation (WHO). Deafness and hearing loss . Geneva, https://www.who.int/news-room/fact-sheets/detail/deafness-and-hearing-loss (26 February 2025, accessed 27 April 2025). Liao BS, Byl FM, Adour KK. Audiometric Comparison of Lassa Fever Hearing Loss and Idiopathic Sudden Hearing Loss: Evidence for Viral Cause. Otolaryngol Neck Surg 1992; 106: 226–229. https://doi.org/10.1177/019459989210600303 Cummins D, McCormick JB, Bennett D, et al. Acute sensorineural deafness in Lassa fever. JAMA 1990; 264: 2093–2096. Ibekwe TS, Okokhere PO, Asogun D, et al. Early-onset sensorineural hearing loss in Lassa fever. Eur Arch Otorhinolaryngol 2011; 268: 197–201. https://doi.org/10.1007/s00405-010-1370-4 Mishra B, Ranjan J, Purushotham P, et al. High proportion of low cycle threshold value as an early indicator of COVID-19 surge. J Med Virol 2022; 94: 240–245. https://doi.org/10.1002/jmv.27307 Yun NE, Ronca S, Tamura A, et al. Animal Model of Sensorineural Hearing Loss Associated with Lassa Virus Infection. J Virol 2016; 90: 2920–2927. https://doi.org/10.1128/JVI.02948-15 Zhu Y, Li G, Zhuang H, et al. Meta-Analysis Comparing Steroids and Diuretics in the Treatment of Acute Low-Tone Sensorineural Hearing Loss. Ear Nose Throat J 2021; 100: 281S-285S. https://doi.org/10.1177/0145561319869610 Saka SA, Akhigbe T, Nwosu L, et al. Unraveling the Mechanisms of Hearing Loss in Lassa Fever: A Pathophysiological and Clinical Perspective. Asian J Res Infect Dis 2025; 16: 41–46. https://doi.org/10.9734/ajrid/2025/v16i3429 Additional Declarations The authors declare no competing interests. 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Report\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLassa fever is an acute viral haemorrhagic illness caused by the Lassa virus, endemic in West Africa and affecting tens of thousands of individuals annually, with Nigeria bearing a substantial share of the burden [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The Africa Centres for Disease Control and Prevention estimates that 100,000 to 300,000 Lassa fever infections occur each year, resulting in over 5,000 deaths, mostly in Nigeria, Sierra Leone, Guinea, Benin, Ghana, Mali, and Liberia. Notably, Nigeria alone accounts for approximately 75% of global Lassa fever cases annually [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In 2024, the Nigeria Centre for Disease Control (NCDC) reported 1,309 confirmed cases and 214 deaths, with Edo State accounting for nearly 30% of the confirmed cases nationwide [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough many patients recover with appropriate care, a subset of survivors experience long-term complications, among which sensorineural hearing loss (SNHL) is particularly debilitating. Studies have shown that SNHL affects approximately 13\u0026ndash;33% of Lassa fever survivors [\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9 CR10 CR11\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Despite progress in acute management, the post-recovery burden of Lassa fever, especially hearing impairment remains poorly characterized and under-addressed. SNHL can severely affect communication, educational attainment, occupational productivity, social engagement, and mental well-being [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The impact is especially profound in resource-limited settings like Edo State, where access to audiological services and rehabilitative care is scarce. In such contexts, children with hearing impairment risk academic under-performance, while adults face economic hardship and social isolation, further entrenching poverty. Globally, disabling hearing loss affects over 430\u0026nbsp;million people, a figure projected to nearly double by 2050, according to the World Health Organization. Therefore, integrating hearing loss surveillance into Lassa fever control programs is essential for holistic survivor management and strengthening health systems in endemic regions [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis case report underscores the potential role of pharmacologic intervention in managing post-Lassa fever sensorineural hearing loss (SNHL), a commonly overlooked complication with significant public health implications. Survivors of Lassa fever remain vulnerable to preventable disabilities that diminish quality of life and compound the socioeconomic burden in low-resource settings. Understanding and addressing such sequelae is essential for equitable infectious disease management. To date, no pharmacological intervention has been shown to reverse or improve Lassa-induced SNHL. Previous reports consistently describe poor outcomes, with most patients experiencing permanent hearing loss [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. For example, one study observed no recovery in acute severe SNHL cases treated after the active phase of Lassa fever [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In contrast, our patient demonstrated significant functional recovery following early initiation of mannitol, hydrocortisone, betahistine, and neurovite, suggesting that timely combination therapy may alter prognosis. This distinction underscores the uniqueness of our case and its potential contribution to advancing therapeutic strategies for post-Lassa SNHL.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 13-year-old girl who was managed for Lassa fever disease for 2 weeks, confirmed by polymerase chain reaction (PCR) test and was discharged home after the Lassa PCR result showed Negative. Two days post discharge, patient presented with a febrile illness and was admitted in Children Emergency (CHER) Ward, managed for Malaria to rule out Lassa fever, however, repeated Lassa PCR was not significant (high cycle threshold values) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Since she was stable, the patient was discharged home. Two days post-discharge, patient developed sudden profound hearing loss of the right ear and presented to otolaryngology clinic four days after the onset of hearing loss. Patient was admitted and examined. Voice test conducted and patient didn't respond to whisper, conversation and loud voice while the left ear was closed by pressing on the tragus. Weber test was done and sound lateralized to the unaffected (left) ear. Otoscopic examination revealed normal findings in both ears. Pure tone audiometry (PTA) could not be done at presentation as service were not available.\u003c/p\u003e\u003cp\u003eOn admission, patient was placed on intravenous (IV) mannitol at 2g/kg over 30mins and then repeated after 8 hours, IV hydrocortisone 2mg/kg 8hourly, Tab betahistine 8mg 12hourly and Tab neurovite one tablet 12hrly. Sixteen (16) hours on admission, mother informed us that the patient could hear on the affected ear. She was further examined and patient responded to loud voice. Then PTA was done as reported in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, with a right pure tone average of 102dB and left pure tone average of 25dB (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003ePatient was discharged home on Tabs prednisolone, betahistine and neurovite. Three days following discharge, she complained of persistent tinnitus and peppery sensation in the affected right ear and increased sensitivity to normal everyday sounds, suggestive of hyperacusis, nerve irritation or acoustic trauma. Repeated PTA one-week post-discharge showed increased pure tone average in the left ear (47dB) and reduced pure tone average in the right ear (80dB) as show in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eOne-month post-discharge pure tone average revealed 43dB in the left and 57dB in the right (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSummary of pure tone average\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e16 hours on admission\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e1-week post-discharge\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u003cp\u003e1-month post-discharge\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePure Tone Average\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRight Ear\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLeft Ear\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eRight Ear\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eLeft Ear\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003eRight Ear\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLeft Ear\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e102dB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25dB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e80dB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e47dB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e57dB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e43dB\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case highlights important clinical and public health considerations regarding post-Lassa fever complications, particularly sensorineural hearing loss (SNHL). One of the key findings from this case is the development of profound right-sided hearing loss in a patient recently discharged after Lassa fever treatment, despite having a high cycle threshold (Ct) value on PCR, typically interpreted as low viral load [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. This challenges the current practice of discharging patients solely based on viral load. Our findings suggest that a low level of circulating virus, as indicated by high Ct values, does not preclude the development of significant sequelae such as SNHL. Thus, discharging patients solely on account of low viral load should be discouraged until comprehensive post-recovery evaluations, including auditory screening, are conducted. Additionally, the sudden increase in the pure tone average (PTA) in the unaffected (left) ear from 25 to 47 dB raises concerns about subclinical or evolving bilateral auditory involvement, possibly due to ongoing viral or immune-mediated inner ear pathology. This indicates that Lassa virus activity or its sequelae may persist beyond the viraemic phase and may not be fully captured by PCR Ct values. Hence, early audiological intervention is necessary, and routine hearing assessments should be incorporated into the follow-up of all Lassa fever survivors, especially in endemic areas.\u003c/p\u003e\u003cp\u003eThe pathogenesis of sensorineural hearing loss in Lassa fever is not clear. However, it has been suggested in some studies that the hearing loss results from an exaggerated immune response against the inner ear structures [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In another study using the mouse model, damage to cochlear hair cell and degeneration of the spiral ganglion cells of the auditory nerve, thinning of the stria vascularis were observed. Distension of the Reisners membrane, infiltration of blood cells within the scala tympani and minor loss of inner and outer hair cells were also seen [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. This case underscores the need for research to determine the level of Lassa viral load that becomes cytotoxic to cochlear and neural structures. While Ct values provide an estimate of viral burden, the precise threshold at which the virus initiates irreversible auditory damage remains undefined. Establishing this threshold would not only enhance our understanding of viral pathogenesis but also help refine discharge criteria and survivor monitoring protocols.\u003c/p\u003e\u003cp\u003eThe positive response to IV mannitol and hydrocortisone in this case suggests that endolymphatic hydrops and inflammation may play roles in the pathogenesis of Lassa-related SNHL. Mannitol, an osmotic diuretic, could help reduce intracochlear pressure, while hydrocortisone likely exerts anti-inflammatory effects that reduce neural injury. Additionally, betahistine, a histamine analogue, may improve inner ear blood flow through vasodilation, and neurovite (a vitamin B complex) may support nerve regeneration. These mechanisms align with existing approaches and empiric protocols to managing ototoxic and inflammatory hearing loss [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Although the exact pathophysiology of Lassa-induced hearing impairment remains unclear, previous studies have proposed four plausible mechanisms: direct viral invasion of the cochlea, immune-mediated cochleitis, cochlear ischemia, and vascular compromise, all of which are compatible with the clinical progression observed in this case [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eGiven the potential benefits observed with the combination of betahistine, prednisolone, and neurovite in patients with post-Lassa SNHL, we suggest that further research should explore the prophylactic use of these agents in all Lassa survivors at pre and post-discharge. This strategy could be especially valuable in settings where routine audiological screening is unavailable. While the routine inclusion of these agents in discharge medications may hold promise for preventing or mitigating delayed-onset hearing loss, this approach require validation through randomized controlled trials before formal adoption into treatment guidelines. Early intervention may prevent permanent damage; however, many patients present late, when neural injury has already become irreversible. Consequently, survivor follow-up must prioritize early screening, especially in rural and low-resource settings where auditory care is limited.\u003c/p\u003e\u003cp\u003eAlthough the clinical presentation strongly suggests Lassa-induced SNHL, alternative causes must be considered. Malaria, for which the patient was briefly treated, can rarely cause hearing impairment, but her normal otoscopic findings and temporal association with recent Lassa infection make this less likely. Ototoxic drug exposure was excluded as the patient did not receive aminoglycosides or other known ototoxins during hospitalization. Idiopathic sudden SNHL remains a possibility; however, the onset immediately following confirmed Lassa fever, combined with the absence of other systemic causes, supports a Lassa-related aetiology. These considerations strengthen the causal inference while acknowledging diagnostic uncertainty inherent to single-case reports.\u003c/p\u003e\u003cp\u003eBeyond this case, there are increasing anecdotal reports from otolaryngologists in endemic regions of sudden hearing loss following febrile illnesses, which remain a diagnostic challenge. While many of these cases may be unrecognized sequelae of Lassa fever, they are often not evaluated due to lack of confirmatory diagnostics and audiological infrastructure. These patterns suggest that the true burden of post-infectious hearing loss may be under-reported, and the link between febrile illnesses and SNHL in endemic areas remains a puzzle yet to be fully unravelled. Despite the growing recognition of these complications, auditory research in Lassa fever survivors is grossly underfunded. There is a compelling need for investment in rural hearing services, including routine audiometric screening, community-based rehabilitation programs, training of audiology personnel, and subsidization of hearing aids and cochlear implants. As many SNHL cases caused by Lassa virus are irreversible due to late presentation, affordable access to assistive devices like cochlear implants is critical, especially in low-resource settings.\u003c/p\u003e\u003cp\u003eThis report has several limitations. First, it represents a single case, limiting generalizability. Second, baseline audiometry prior to Lassa infection was not available, precluding absolute confirmation of new-onset hearing loss. Third, advanced imaging (e.g., MRI or CT) was not performed, which could have excluded structural or vascular causes of SNHL. Despite these limitations, the temporal relationship between Lassa fever recovery and onset of profound SNHL, coupled with treatment response, provides valuable clinical insights.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case adds to the growing evidence that post-Lassa fever hearing loss is an urgent and under-addressed public health issue. A multi-pronged approach involving early diagnosis, pharmacologic research, auditory rehabilitation, and policy-driven investment is essential to reduce preventable disability among survivors and to improve long-term outcomes in Lassa-endemic regions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMA led patient management and contributed to the writing, editing and review of the final manuscript.\u003c/p\u003e\n\u003cp\u003eFFB led patient management and contributed to the writing, editing and review of the final manuscript.\u003c/p\u003e\n\u003cp\u003eSAS conceptualized, drafted the original manuscript, edited, reviewed the manuscript and managed patient under supervision of FFB and MA.\u003c/p\u003e\n\u003cp\u003eMU conducted audiometry and contributed to writing and reviewing of final manuscript.\u003c/p\u003e\n\u003cp\u003eEO, DA, JO, OJE, and EA contributed to the writing, editing and review of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur institution does not require ethical approval for reporting individual cases or case series.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of her clinical details and/clinical images was obtained from the legal guardian. A copy of the consent form is available for review by the Editor of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the information about the patient is in the medical record with the clinicians (FFB and SAS) participating in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case report was prepared in accordance with CARE (CAse REport) guidelines to ensure transparency and completeness. The completed CARE checklist has been attached as a supplementary file\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWorld Health Organisation (WHO). \u003cem\u003eLassa fever - Nigeria\u003c/em\u003e. World Health Organisation (WHO), https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON463 (2023, accessed 26 May 2026).\u003c/li\u003e\n\u003cli\u003eAfrica Centers for Disease Control and Prevention. \u003cem\u003eLassa fever\u003c/em\u003e. Africa CDC, https://africacdc.org/disease/lassa-fever/ (2018, accessed 26 May 2025).\u003c/li\u003e\n\u003cli\u003eNigeria Centre for Disease Control and Prevention (NCDC). \u003cem\u003eLassa Fever Situation Report\u003c/em\u003e. NCDC: NCDC, https://www.ncdc.gov.ng/themes/common/files/sitreps/a45a720bd6ddd1e75a5a3e7e6195e412.pdf (December 2024, accessed 27 April 2025).\u003c/li\u003e\n\u003cli\u003eReliefweb. 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Meta-Analysis Comparing Steroids and Diuretics in the Treatment of Acute Low-Tone Sensorineural Hearing Loss. \u003cem\u003eEar Nose Throat J\u003c/em\u003e 2021; 100: 281S-285S. https://doi.org/10.1177/0145561319869610\u003c/li\u003e\n\u003cli\u003eSaka SA, Akhigbe T, Nwosu L, et al. Unraveling the Mechanisms of Hearing Loss in Lassa Fever: A Pathophysiological and Clinical Perspective. \u003cem\u003eAsian J Res Infect Dis\u003c/em\u003e 2025; 16: 41\u0026ndash;46. https://doi.org/10.9734/ajrid/2025/v16i3429\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Irrua Specialist Teaching Hospital","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Lassa Fever, Hearing Loss, Sensorineural, Audiometry, Pure-Tone, Viral Hemorrhagic Fevers, Post-Infectious Complications, Mannitol, Hydrocortisone, Betahistine","lastPublishedDoi":"10.21203/rs.3.rs-7697165/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7697165/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eLassa fever is a viral haemorrhagic illness endemic in West Africa, with Nigeria accounting for a significant proportion of global cases. While most patients recover, sensorineural hearing loss (SNHL) is a serious and often overlooked post-infectious complication. We present the case of a 13-year-old girl who developed sudden profound right-sided SNHL shortly after recovering from Lassa fever, despite a high cycle threshold (Ct) value on PCR, indicating low viral load. She was treated with intravenous mannitol and hydrocortisone, along with oral betahistine and neurovite, and demonstrated notable improvement in hearing over a one-month period. Follow-up revealed subclinical involvement of the contralateral ear, emphasizing the risk of bilateral progression. This case underscores that significant auditory sequelae can occur even at low viral loads and highlights the potential benefits of early pharmacologic intervention. It also reinforces the urgent need for routine hearing assessment and auditory rehabilitation in Lassa fever survivors.\u003c/p\u003e","manuscriptTitle":"A Promising Therapeutic Approach for Post-Lassa Fever Sensorineural Hearing Loss: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-25 06:40:27","doi":"10.21203/rs.3.rs-7697165/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7657edf5-7653-4b3d-bc41-c9f37d018265","owner":[],"postedDate":"September 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":55222267,"name":"Virology"},{"id":55222268,"name":"Infectious Diseases"}],"tags":[],"updatedAt":"2025-09-25T06:40:27+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-25 06:40:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7697165","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7697165","identity":"rs-7697165","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}