Hearing loss in individuals at risk for neurosyphilis

Abstract

Otosyphilis is a serious complication of syphilis.

329 participants enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis underwent portable audiometry (250 Hz to 8000 Hz at 5–75 dB); it was repeated in 33 after otosyphilis treatment. Treponema pallidum spp pallidum (T. pallidum) DNA in blood was quantitated by polymerase chain reaction. Odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were determined by logistic, ordinal or Cox regression.

166 (50.5%) had normal hearing; 15 (4.6%) had low frequency (LF) loss alone, 93 (28.3%) had high frequency (HF) loss alone, and 55 (16.7%) had both. Adjusted odds of any hearing loss were higher with detectable blood T. pallidum DNA (3.00 [1.58–5.69], p = 0.001), CSF pleocytosis (2.02 [1.12–3.66], p = 0.02), and older age (2.22 per 10-year increase, [1.70–2.91], p < 0.001). HRs of normalization of LF and HF loss were lower for older individuals (0.20 [0.07–0.63, p = 0.005] and 0.22 [0.05–0.94, p = 0.04]), and HRs for normalization of HF loss were lower for those with more severe loss (0.09 [0.02–0.43], p = 0.002), and in those with CSF pleocytosis (0.32 [0.11–0.96], p = 0.04).

Older age and CSF pleocytosis increase the likelihood of otosyphilis and impair hearing recovery after otosyphilis treatment.

Keywords

Syphilis hearing loss otosyphilis

Introduction

Since 2000, cases of syphilis have dramatically increased in the US, Europe and Asia.^1–3 As syphilis has increased, so has complicated syphilis.^4–6 Otosyphilis, or hearing loss due to syphilis, is an important complication of syphilis, but less is known about it, largely because few studies have systematically addressed the problem in individuals with active syphilis.⁷ For example, studies from the 1980s and 1990s defined otosyphilis as reactive serum fluorescent treponemal antibody absorption test and hearing loss of unknown etiology; only 22% of patients who met these criteria actually had otosyphilis.⁸

Over the last two decades, small series and case reports have addressed the clinical manifestations of otosyphilis. A retrospective analysis of 85 individuals found that the most common symptoms of otosyphilis were insidious onset of bilateral mild or moderate symmetrical or asymmetrical sensorineural hearing loss.⁹ However, the serum Venereal Disease Research Laboratory (VDRL) was nonreactive or weakly reactive in 27.1%, and the median titer was 1:2, suggesting that most patients did not have active syphilis. Subsequent case reports describe bilateral or unilateral hearing loss,^10–13 that may be sudden in onset,^12,14 often in persons living with HIV (PLWH),^11–13 sometimes with concomitant ocular syphilis.^12,14–17 A recent series of 12 patients with syphilis and hearing loss who underwent formal audiometry found that the most common presentation was bilateral, asymmetric, mild or moderate high frequency sensorineural hearing loss.¹⁸ Residual hearing loss after otosyphilis treatment is often reported.^10–13 Here we report results of portable audiometry in 329 individuals enrolled in a study of CSF abnormalities in active syphilis, 33 of whom had hearing loss and were reexamined after otosyphilis treatment.

Methods

Study participants

Participants were enrolled in a study of CSF abnormalities in syphilis conducted in Seattle, WA, USA.¹⁹ Eligibility for enrollment included clinical and serological evidence of syphilis and concern for neurosyphilis by the referring provider or by the patient. Reasons for referral to the study included, but were not restricted to 1) neurological symptoms or signs, particularly vision or hearing loss; 2) serum Rapid Plasma Reagin (RPR) titer ≥ 1:32; or 3) in PLWH, peripheral blood CD4+ T cell count ≤ 350 cells/ul. Study participants were eligible to re-enter the study with subsequent episodes of syphilis if they met entry criteria. If a participant underwent portable audiometry at more than one entry visit, only the results at the first of these were considered. Between 10/30/2008 and 7/2/2013, 394 consecutive individuals underwent portable audiometry. The 329 individuals included in the analysis underwent portable audiometry in both ears, did not have pre-existing hearing complaints, had reactive serum nontreponemal and treponemal serological tests, and had available information regarding syphilis stage, CSF white blood cell (WBC) count and CSF-VDRL results (Figure 1). In individuals with CSF pleocytosis or reactive CSF-VDRL, no etiologies other than neurosyphilis (such as opportunistic infections) were identified. Individuals who were treated for neurosyphilis with intravenous penicillin G or intramuscular aqueous procaine penicillin G plus oral probenecid according to US Centers for Disease Control and Prevention (CDC) guidelines²⁰ (and which are also the recommended treatments for otosyphilis) underwent follow-up audiometry at 3, 6, and 12 months after therapy.

Figure 1.

Selection of participants included in the analysis. CSF, cerebrospinal fluid; RPR, Rapid Plasma Reagin; VDRL, Venereal Disease Research Laboratory.

Clinical procedures

Participants underwent a standardized medical history and physical examination, blood draw, and lumbar puncture. Hearing levels at 250 Hz to 8000 Hz at 5–75 dB were assessed in both ears using a portable audiometer (Audiology Technology, Kent, WA). Hearing level was set at 80 dB for each frequency at which the tone could not be heard. Low frequency pure tone average (PTA) for each ear was calculated for 500, 1000 and 2000 Hz, and high frequency PTA was calculated for 4000, 6000 and 8000 Hz. PTAs >25 dB were considered abnormal. Participants with unilateral or bilateral abnormal low frequency PTAs are termed as those with low frequency hearing loss, and those with unilateral or bilateral abnormal high frequency PTAs are termed as those with high frequency hearing loss. Those with both low and high frequency loss are termed as having combined hearing loss. Severity of low and high frequency loss was defined by the highest PTA (low or high frequency) of the two ears, and was categorized as none (less than 26 dB), mild (26–40 dB), moderate (41–55 dB), moderately severe (56–70 dB) or severe (greater than 71 dB). The study protocol was reviewed and approved by the University of Washington institutional review board, and written informed consent was obtained from all participants.

Laboratory methods

Cerebrospinal fluid WBC enumeration and CSF-VDRL reactivity were determined in a CLIA-certified hospital clinical laboratory. HIV RNA concentration and peripheral blood CD4+ T lymphocyte counts were obtained by review of medical records, and only values obtained within 90 days of hearing assessment were considered. Serum RPR titers were performed in a research laboratory using published methods.²¹ Quantitative detection of Treponema pallidum subspecies pallidum (T. pallidum) DNA in blood (n = 295; limit of detection 5 copies per ml) and qualitative detection of T. pallidum rRNA in CSF (n = 329) were determined as previously described.^19,22

Statistical methods

Descriptive statistics are expressed as number (percent) or median (interquartile range [IQR]). Proportions were compared by the Chi-square or Fisher's exact test. Odds ratios (ORs) with 95% confidence intervals (95% CI) were determined by binomial or ordinal logistic regression. Covariates with p-values ≤0.10 were included in multivariate analyses to determine adjusted ORs (aORs). Normalization of hearing loss was defined as decline in PTA to 25 dB or less. Percent normalization was determined by Kaplan Meier analysis. Hazard ratios (HR) for normalization with 95% CIs were determined using Cox regression. P-values <0.05 were considered statistically significant.

Results

Participants and hearing loss

The characteristics of the study participants are shown in Table 1. Their demographic features reflect the demographics of syphilis in Seattle and King County, Washington, during the study period.²³ As such, most of the 329 participants were men; 81.8% were PLWH, reflecting the higher rates of syphilis in PLWH²³ and increased concern regarding neurosyphilis in these individuals based on then current CDC guidelines.^24,25 One hundred seventy-seven were treated for their current episode of syphilis a median of 7 (5–14) days before their hearing assessment. Seventy-three (22.2%) complained of new hearing loss. One hundred sixty-six (50.5%) had normal low and high frequency PTAs, 15 (4.6%) had low frequency loss alone, 93 (28.3%) had high frequency loss alone, and 55 (16.7%) had both. Low frequency loss alone was largely unilateral, while high frequency loss alone or combined loss were both unilateral and bilateral (Figure 2). Among the 27 individuals with bilateral low frequency loss, all were symmetrical (less than a 15 dB difference at all three frequencies). Among the 82 individuals with bilateral high frequency loss, 10 (12.2%) were asymmetrical (a difference of at least 15 dB at all three frequencies).

Table 1.

Characteristics of 329 participants.

Characteristic	Number (%) or median (IQR)
Men	325 (98.8)
Age (years)	41 (32–48)
PLWH	269 (81.8)
On ARVs	184 (68.4)
Peripheral blood CD4+ count (cells/ul)^a	438 (283–607)
Plasma HIV RNA ≤ 50 copies/ml^b	115 (49.1)
Syphilis stage
Primary	33 (10.0)
Secondary	124 (37.7)
Early latent	96 (29.2)
Late latent	76 (23.1)
Serum RPR titer	64 (32–256)
T. pallidum DNA detected in blood^c	67 (22.7)
Treatment for current episode of syphilis before hearing assessment	177 (53.8)
Reactive CSF-VDRL	37 (11.2)
CSF WBCs > 10/ul	86 (26.1)
T. pallidum rRNA detected in CSF	30 (9.1)

^an = 231.

^bn = 234.

^cn = 295.

ARVs, antiretrovirals; CSF, cerebrospinal fluid; PLWH, persons living with HIV; RPR, Rapid Plasma Reagin; VDRL, Venereal Disease Research Laboratory; WBC, white blood cells.

Figure 2.

Stacked bar graph showing the number of participants with abnormal low frequency (LF) pure tone average (PTA) in one or both ears, abnormal high frequency (HF) PTA in one or both ears, and both abnormal low and high frequency PTAs in one or both ears. Solid bars indicate unilateral abnormality and shaded bars indicate bilateral abnormality (high, high frequency; low, low frequency).

Among the variables in Table 1, age differed significantly between the three patterns of hearing loss: median (IQR) age for low frequency loss was 38 (27–43), high frequency loss was 44 (39–52), and combined loss was 48 (42–57) (p < 0.001). The proportion of individuals with CSF pleocytosis (defined as >10 WBCs/ul) was similar in those with high frequency or combined loss (32 [34.4%] of 93 vs. 20 [36.4%] of 55, p = 0.81), but was significantly lower in those with low frequency loss (1 [6.7%] of 15, p = 0.03 compared to high frequency and combined together). None of the other variables in Table 1 differed by pattern of hearing loss.

As expected because of the frequencies of human speech, individuals who complained of new hearing loss were more likely to have low or combined loss than high frequency loss alone (31 [44.3%] of 70 vs. 21 [22.6] of 93, p = 0.003). Conversely, 21 (28.8%) of 73 individuals who complained of new hearing loss had normal portable audiometry. Severity of hearing loss was greater for high frequency than for low frequency loss. While the severity of hearing loss for all 15 participants (100%) with low frequency loss alone was mild, severity of 30 (32.3%) of 93 with high frequency loss alone was moderate or greater (p = 0.01). Similarly, among the 55 individuals with combined loss, severity of the low frequency component was mild in 50 (90.9%), while severity of the high frequency component was moderate or greater in 38 (69.1%, p < 0.001).

Any hearing loss (abnormal LF PTA, HF PTA, or both) was more common in PLWH compared to HIV-uninfected (142 [52.8%] of 269 vs. 21 [35.0%] of 60, p = 0.01). Among the PLWH, any hearing loss was not related to peripheral blood CD4+ T cell or plasma HIV RNA concentrations or current use of antiretroviral agents. Age was significantly higher in individuals with any hearing loss compared to those without (44 [38–53] vs. 37 years [29–43], p < 0.001). Severity of any high frequency hearing loss was also greater in older individuals; for every 10-year increase in age, the odds of increased severity of hearing loss increased by 2.81 ([2.21–3.56], p < 0.001). This relationship could not be tested for any low frequency loss because only 5 (7.1%) of the 70 individuals had greater than mild loss.

Hearing loss, syphilis and neurosyphilis

We first examined relationships between syphilis-related variables and hearing loss. The odds of any hearing loss were higher in those with higher serum RPR titers, not treated for the current syphilis episode before hearing assessment, and with detectable T. pallidum DNA in blood (Table 2). In multivariate analysis including all three of these variables, the adjusted odds of any hearing loss remained significantly higher in individuals who had T. pallidum DNA detected in blood (Table 2). Among the 67 individuals with detectable T. pallidum DNA in blood, there was a trend toward higher median number of DNA copies per ml in those with, compared to those without, any hearing loss (165.0 [59.0–414.8] vs. 85.6 [12.5–368.2] copies/ml, p = 0.08).

Table 2.

Syphilis- and neurosyphilis-related factors associated with any hearing loss or severity of high frequency hearing loss.

	Any hearing loss^a		Severity of high frequency hearing loss^b
Factor	OR (95% CI), p-value	aOR (95% CI), p-value	OR (95% CI), p-value	aOR (95% CI), p-value
Syphilis related
Early vs. late stage syphilis	1.38 (0.82–2.31), p = 0.22	NI^c	1.14 (0.68–1.89), p = 0.61	NI
Serum RPR titer per 2-fold increase in titer	1.18 (1.06–1.31), p = 0.002	NI	1.20 (1.08–1.33), p<0.001	1.13 (1.01–1.26), p = 0.04
Treatment for current episode of syphilis before hearing assessment	0.65 (0.42–1.01), p = 0.06	NI	0.63 (0.42–0.96), p = 0.03	NI
T. pallidum DNA detected in blood	3.81 (2.09–6.95), p<0.001	3.81 (2.09–6.95), p<0.001	3.27 (1.96–5.45), p<0.001	2.83 (1.67–4.79), p<0.001
Neurosyphilis related
Reactive CSF-VDRL	1.78 (0.88–3.60), p = 0.11	NI	2.18 (1.15–4.14), p = 0.02	NI
CSF WBCs > 10/ul	1.94 (1.18–3.21), p = 0.01	1.69 (1.00–2.84), p = 0.05	2.46 (1.54–3.92), p<0.001	2.17 (1.34–3.51), p = 0.002
T. pallidum rRNA detected in CSF	3.08 (1.33–7.14), p = 0.009	2.53 (1.06–6.00), p = 0.04	2.97 (1.47–6.03), p = 0.002	2.21 (1.07–4.55), p = 0.03

^aAny hearing loss is defined as abnormal low frequency pure tone average, high frequency pure tone average or both.

^bSeverity of high frequency hearing loss was categorized as none, mild, moderate, or greater than moderate.

^cNI, not included in the final multivariate model because p > 0.10 in univariate analysis or p > 0.05 in the initial multivariate model.

Odds ratios (ORs) and adjusted ORs (aORs) for any hearing loss were determined by binomial logistic regression, and ORs and aORs for severity of high frequency loss were determined by ordinal logistic regression.

CSF, cerebrospinal fluid; RPR, Rapid Plasma Reagin; VDRL, Venereal Disease Research Laboratory; WBC, white blood cells.

We then examined relationships between neurosyphilis-related variables and hearing loss. The odds of any hearing loss were higher in individuals with CSF pleocytosis or detection of T. pallidum rRNA in CSF (Table 2). When both these covariates were included in multivariate analysis, the adjusted odds of hearing loss remained significantly higher in those with detection of T. pallidum rRNA in CSF and showed a trend toward significance for those with CSF pleocytosis (Table 2).

The odds of greater severity of high frequency hearing loss were higher in those with higher serum RPR titers, and in those with detectable T. pallidum DNA in blood (Table 2). In multivariate analysis, both covariates remained significant (Table 2). Similarly, the odds of greater severity of high frequency loss were higher in those with detectable T. pallidum rRNA in CSF and with CSF pleocytosis (Table 2). In multivariate analysis, both covariates remained significant (Table 2). We could not examine these relationships in those with low frequency loss because few individuals had more than mild severity of low frequency loss.

Is hearing loss or severity of high frequency loss related to HIV, age, syphilis, neurosyphilis or a combination?

Compared to HIV-uninfected, PLWH had higher serum RPR titers (64 [32–128] vs. 128 [32–256], p = 0.008) and were older (33 [24–44] vs. 42 [35–48], p < 0.001). We repeated the analyses investigating the relationship between hearing loss or severity of high frequency loss, and syphilis- and neurosyphilis-related variables that were significant in the multivariate models (Table 2), including HIV status, serum RPR titer and age (Table 3). We included serum RPR titer because of its association with HIV status. The adjusted odds of any hearing loss or severity of hearing loss were not higher in PLWH and were not related to serum RPR titer (Table 3). In the syphilis analyses, the adjusted odds of hearing loss and of greater severity of high frequency hearing loss were significantly higher in those with detectable T. pallidum DNA in blood, and in older participants (Table 3). In the neurosyphilis analyses, the adjusted odds of hearing loss and of greater severity of high frequency hearing loss were significantly higher in those with CSF pleocytosis, and in older participants (Table 3). Interaction terms between age and detectable T. pallidum DNA in blood, and between age and CSF pleocytosis were not significant (data not shown).

Table 3.

Syphilis- and neurosyphilis-related factors associated with hearing loss or severity of high frequency hearing loss taking into account HIV status and age.

	Any hearing loss^a	Severity of high frequency hearing loss^b
Factor	aOR (95% CI), p-value	aOR (95% CI), p-value
Syphilis related
Serum RPR titer per 2-fold increase in titer	NI^c	NI
T. pallidum DNA detected in blood^b	3.22 (1.71–6.06), p < 0.001	2.64 (1.55–4.49), P < 0.001
Person living with HIV	NI	NI
Age per 10-year increase	2.16 (1.66–2.81), p < 0.001	2.77 (2.15–3.58), p < 0.001
Neurosyphilis related
Serum RPR titer per 2-fold increase in titer	NI	NI
CSF WBCs > 10/ul	2.23 (1.28–3.89), p = 0.005	2.98 (1.81–4.88), p < 0.001
T. pallidum rRNA detected in CSF	NI	NI
Person living with HIV	NI	NI
Age per 10-year increase	2.35 (1.82–3.04), p < 0.001	2.90 (2.28–3.70), p < 0.001

^aAny hearing loss is defined as abnormal low frequency pure tone average, high frequency pure tone average or both.

^bSeverity of high frequency hearing loss was categorized as none, mild, moderate, or greater than moderate.

^cNI, not included in the final multivariate model because p > 0.05 in the initial multivariate model.

Adjusted ORs (aORs) for any hearing loss were determined by multivariate binomial logistic regression, and aORs for severity of high frequency loss were determined by multivariate ordinal logistic regression.

CSF, cerebrospinal fluid; RPR, Rapid Plasma Reagin; WBC, white blood cells.

Finally, we examined whether age and covariates related to syphilis and neurosyphilis contributed independently to the risk of any hearing loss and severity of high frequency loss when included in the same analysis. The results were remarkably similar. The adjusted odds of any hearing loss were significantly higher in those with detectable T. pallidum DNA in blood (aOR 3.00 [1.58–5.69], p = 0.001), in those with CSF pleocytosis (aOR 2.02 [1.12–3.66], p = 0.02), and in those with increasing age (aOR 2.22 per 10-year increase [1.70–2.91], p < 0.001). Similarly, the adjusted odds of more severe high frequency hearing loss were significantly higher in those with detectable T. pallidum DNA in blood (aOR 2.37 [1.38–4.06], p = 0.002), in those with CSF pleocytosis (aOR 2.66 [1.58–4.50], p < 0.001), and in those with increasing age (aOR 2.85 per 10-year increase [2.20–3.69], p < 0.001).

Normalization of hearing loss after neurosyphilis treatment

Thirty-three individuals with any hearing loss underwent follow-up portable audiometry after recommended otosyphilis treatment²⁰; 31 had any high frequency hearing loss, and 16 had any low frequency hearing loss. The proportion of individuals in whom any hearing loss normalized was 44.9%; any high frequency loss normalized in 44.5%, and any low frequency loss normalized in 57.8%. The hazard ratios of normalization of any high frequency or any low frequency loss were significantly lower for individuals greater than the median age of the entire study group (n = 329; 41 years) compared to those ≤ 41 (0.20 [0.07–0.63, p = 0.005] and 0.22 [0.05–0.94, p = 0.04]). Because individuals with hearing loss were older than those without, 24 of 33 (73%) individuals in the follow-up analyses were over 41 years of age.

Among those with high frequency loss, the HR of normalization was significantly lower for those with moderate or greater severity of loss (0.09 [0.02–0.43], p = 0.002), and in those with CSF pleocytosis (0.32 [0.11–0.96], p = 0.04). Too few individuals with low frequency hearing loss had more than mild severity loss to allow severity to be considered in an analysis, and there was no relationship between CSF pleocytosis and normalization of low frequency loss (data not shown). Detection of T. pallidum rRNA in CSF or DNA in blood were not related to normalization of high or low frequency loss (data not shown).

Discussion

Otosyphilis is a poorly understood complication of syphilis. We tested 329 individuals at risk for neurosyphilis for hearing loss by portable audiometry. We found that, while only 22.5% complained of new hearing loss in the setting of a new syphilis diagnosis, 49.5% had abnormal portable audiometry, most commonly high frequency and combined low and high frequency loss. Hearing loss was not related to syphilis stage. In multivariate analysis, hearing loss was not related to HIV. It was more common in individuals with detectable T. pallidum DNA in blood, and in those with CSF pleocytosis. Additionally, normalization of hearing loss was less likely in individuals with CSF pleocytosis. Similarly, severity of high frequency loss was greater in those with detection of T. pallidum in blood, and in those with CSF pleocytosis. These findings indicate that the hearing loss that we identified was directly related to active T. pallidum infection and resultant CSF inflammation.

Portable screening audiometry is meant to identify those who should undergo formal audiometry. Because it only assesses air conduction, and it is not performed in a sound proof environment, it may overestimate hearing loss. However, unlike our procedure, the algorithm for screening adult hearing recommended by the American Speech-Language-Hearing Association simply assesses whether a tone can be heard at 25 dB and tests only at 1000, 2000 and 4000 Hz.²⁶ We determined the hearing threshold in dB between 250–8000 Hz for each ear in each participant, and analyzed the results as low and high frequency PTAs. The accuracy of our procedure for correctly identifying hearing loss is supported by the fact that few individuals had low frequency loss; false positive low frequency results occur when testing is performed in a clinic, as we did, rather than a sound proof environment.²⁷ Moreover, we demonstrate associations between hearing loss, severity of loss, and syphilis- and neurosyphilis-related covariates, as well as normalization of hearing loss after otosyphilis therapy.

Current guidelines for screening for otosyphilis suggest querying for symptoms.²⁰ If we had only screened for symptoms, we would have missed more than half of the individuals with abnormal hearing by portable audiometry, in particular, those with high frequency loss alone. Conversely, 21 (28.8%) individuals who complained of new hearing loss had normal portable audiometry. This proportion is similar to what was seen in a smaller series of 12 patients with otosyphilis who underwent formal audiometry.¹⁸

We previously showed that individuals who noted new moderate or greater hearing loss with a new episode of syphilis were significantly more likely to have a reactive CSF-VDRL than individuals with no or mild hearing loss.²⁸ In the current study, the odds of any hearing loss by portable audiometry were not higher in individuals with a reactive CSF-VDRL, but they were significantly higher in individuals with CSF pleocytosis. CSF pleocytosis precedes CSF-VDRL reactivity,²⁹ and it may be that we were identifying individuals, particularly those who did not yet note hearing loss, early in the course of otological involvement.

In addition to syphilis- and neurosyphilis-related factors, we found strong independent associations with age in terms of odds of any hearing loss, and with odds of higher severity of high frequency loss, as well as with likelihood of hearing recovery. Age-related hearing loss, or presbycusis, is common, affecting 25% of individuals ages 55–64 years, and 43% of individuals ages 65–84 years.³⁰ Hearing loss in presbycusis is high frequency, symmetrical and slowly progressive.³¹ The median age of our participants with hearing loss in the cross-sectional analysis was 44, well below the typical age of onset of presbycusis. In addition, the pattern of hearing loss was not characteristic of presbycusis in 43% of participants. It could be argued that increasing age in our cohort increased vulnerability to hearing loss due to syphilis. However, this seems unlikely because the interactions of age with syphilis- and neurosyphilis-related variables were not significant.

Our results suggest that portable audiometry in individuals at high risk for neurosyphilis will identify many patients with unsuspected otosyphilis. Our findings may not be representative of all individuals with syphilis, particularly with regard to the proportion with hearing loss. However, inclusion of individuals who were at increased risk for neurosyphilis enabled us to have sufficient power to identify syphilis- and neurosyphilis-related factors that increase the likelihood of hearing loss, and that influence likelihood of hearing recovery after otosyphilis treatment. There is no reason to believe that these factors would not be applicable to all individuals with syphilis, but future study among unselected persons with syphilis is required for confirmation.

Portable audiometry is quick and easy to perform in the outpatient setting. The modifications that we made to conventional screening audiometry enabled us to identify individuals with syphilis who had hearing loss, and who would have been missed by screening only for symptoms. While ideally these individuals should be referred for evaluation by an audiologist and formal audiological assessments, portable audiometry offers a means to rapidly identify and treat patients with otosyphilis when more detailed assessments are not available.

Footnotes

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

This work was supported by the US National Institute of Neurological Disorders and Stroke (grant # R01 NS34235).

ORCID iD

Christina M Marra

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