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HIV Prevalence in Patients With Syphilis, United States

Blocker, Michael E. MD*†; Levine, William C. MD; St. Louis, Michael E. MD*

Sexually Transmitted Diseases: January 2000 - Volume 27 - Issue 1 - p 53–59
Original Articles

Background: Among persons with a sexually transmitted disease (STD), the proportion who are also infected with HIV is a major factor influencing the public health impact of that STD on HIV transmission.

Goal: To assess HIV infection in persons with syphilis in the United States.

Study Design: A systematic literature review was conducted of U.S. studies with HIV seroprevalence data in patients with syphilis.

Results: Thirty studies were identified and analyzed. The median HIV seroprevalence in men and women infected with syphilis was 15.7% (interquartile range [IQR]: 13.6-21.8%), among men was 27.5% (23.1-29.6%), and among women was 12.4% (8.3-20.5%). Median odds ratios for men and women, men only, and women only were 4.5, 8.5, and 3.3, respectively. Seroprevalences among men who have sex with men (MSM) and injecting drug users (IDU) ranged from 64.3-90.0% and 22.5-70.6%, respectively.

Conclusions: Despite substantial variability, HIV seroprevalence is high among patients with syphilis in the United States, identifying them as a critical target group for HIV prevention efforts.

*From the Epidemiology and Surveillance Branch, Division of STD Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia; and the Division of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina

Financial support for this study was provided by an ATPM/CDC fellowship training grant.

Correspondence and reprint requests: Michael E. Blocker, MD, University of North Carolina, 547 Burnett-Womack, CB# 7030, Chapel Hill, NC 27599-7030.

Received for publication May 14, 1999, revised July 27, 1999, and accepted July 30, 1999.

THE ASSOCIATION BETWEEN sexually transmitted diseases (STDs) and HIV has been well established.1–5 Several studies have shown that the clinical manifestations of certain STDs facilitate the transmission of HIV.6–12 This is true with ulcerative STDs. Herpes infection increases the shedding of HIV in coinfected individuals.13 HIV has been detected in and cultured from the genital ulcers of persons infected with HIV.13–16 In syphilis, the presence of a chancre provides a mechanical break in the protective skin barrier, allowing access to HIV. This is amplified by the increased number of inflammatory cells, the target of HIV, recruited to the syphilitic ulcer, as well as increased expression of HIV from those cells already infected.17,18 This may affect HIV transmission by increasing acquisition in HIV-uninfected individuals and increasing infectiousness in persons infected with HIV. The effects of community-based STD intervention on HIV transmission have been variable,19–20 although potentially a large impact on HIV transmission can be made when appropriate treatment of symptomatic STDs is delivered in a sustained fashion.19 The potential for concomitant STDs to affect HIV transmission is reflected in recent national recommendations for enhanced STD management as one component of a comprehensive HIV prevention strategy.21,22

Syphilis is endemic in several areas of the United States, mostly concentrated in the Southeast. Thirty-one counties account for approximately 50% of cases.23 Outbreaks have recently been reported in North Carolina,24 Maryland,25 and Arizona (Centers for Disease Control and Prevention [CDC], unpublished data). The CDC has begun a national effort to eliminate endemically transmitted syphilis from the United States, based in part on the potential importance of syphilis as a cofactor for HIV transmission.26 This article surveys various published and unpublished studies to assess the degree of HIV infection in individuals with syphilis in recent studies from the United States.

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Literature Review

Articles included in this review were obtained through a MEDLINE literature search from 1985 to 1998, using an OVID search engine. The search was conducted by cross-referencing the terms syphilis, syphilis serodiagnosis, Treponema pallidum, ulcer, genital diseases (male), and genital diseases (female) with the terms HIV, HIV-1, HIV seroprevalence, HIV seropositivity, and HIV infections. Only articles written in English were reviewed. Articles were included from a collection of the literature pertinent to STDs and HIV, maintained by the CDC, Division of STD Prevention. Selected CDC STD outbreak investigation reports and MMWR reports involving syphilis outbreaks were also reviewed. Studies were classified as eligible if they fulfilled all the following criteria: 1) subjects were from the United States, 2) syphilis was categorized by clinical stage of disease (primary, secondary, or latent) or by reactivity of serologic testing, 3) patients were not selected based on HIV status, and 4) data were extractable in a way that allowed determination of HIV seroprevalence among persons with syphilis.

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Data Extraction

All articles eligible for inclusion were read and data extracted as available: 1) the proportion of individuals with primary and secondary syphilis who were HIV seropositive, 2) the proportion of individuals with primary, secondary, or early latent syphilis (early disease) who were HIV seropositive, and 3) the proportion of individuals with reactive syphilis serologic tests who were HIV seropositive.

The data extracted from each article could provide one or more data points for this review. Each study could provide information for the following populations: men and women, men alone, women alone, injecting drug users (IDU), and men who have sex with men (MSM). Several articles presented data from two distinct study populations. In such cases, data were extracted for each population separately.

Eligibility for inclusion did not require HIV seroprevalence data from a referent group. However, when reported in an article, such data were extracted. When possible, the referent groups included only those individuals without syphilis.

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Statistical Measures

Data were expressed as the percentage of individuals who were seropositive for HIV among those with syphilis and those without syphilis. Data were analyzed in three main populations: men and women together, men alone, and women alone. To summarize the central tendency of the data, median percentages within each group were calculated, as well as an interquartile range (25th percentile-75th percentile). Box plots were created to further describe the distribution of the three main groups. In studies for which data was presented on HIV seropositivity in persons without syphilis, odds ratios for HIV seropositivity were calculated, with central tendencies expressed as median odds ratio. Articles that reported on studies that were restricted to two high risk subpopulations, IDU and MSM, were also extracted, but were considered separately; these studies were not included in the descriptive statistics for the more general series of patients with syphilis. Data from these two populations were shown with odds ratios when appropriate.

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Five hundred forty-nine articles were identified by a Medline literature search. Thirty studies were identified from which HIV infection rates in persons with syphilis could be calculated. Twenty-two studies provided 25 data points for men and women. Seven studies provided nine data points for men alone. Eleven studies provided 13 data points for women alone. Three data points were provided for IDU and three for MSM from three and two studies, respectively. The studies investigating IDU did not provide sufficient data to determine sex specific results.

Human immunodeficiency virus coinfection rates by study, risk group, stage of disease, study population, and geographic location are presented in Table 1. The median HIV seroprevalence among men and women with syphilis in the United States was 15.7% (IQR 13.6-21.8%). For men alone, the median HIV seroprevalence was 27.5% (IQR 23.1-29.6%). For women alone, the median HIV seroprevalence was 12.4% (IQR 8.3-20.5%). This is summarized in Table 2. Box and whisker graphs are shown in Figure 1.







Fig. 1

Fig. 1

Comparison groups, for which HIV seroprevalence data in persons without syphilis were calculated, were reported in 17 studies. Fourteen odds ratios were calculated for men and women together (median odds ratio 4.5). Five odds ratios were obtained for men alone (median odds ratio 8.5) and eight odds ratios were obtained for women alone (median odd ratio 3.3). Table 2 shows odds ratios for these groups.

Human immunodeficiency virus seroprevalences for MSM and IDU ranged from 64.3% to 90.0% and 22.5% to 70.6%, respectively. Odds ratios ranged from 5.4-7.4 for MSM and 3.0-3.5 for IDU. These results are shown in Table 3..



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The public health significance of STDs on the U.S. HIV epidemic is influenced by the amount of coinfection present, the effect that coinfection has on HIV transmission, and the prevalence of the STD in the population. While syphilis rates in the United States are at extremely low levels, recent history documents potential for major epidemics, regionally and nationally, in the future. The studies included in this review demonstrate that the HIV infection rate is high in persons with syphilis in the United States. Previous investigations have indicated that coinfected individuals are at elevated risk to transmit HIV. This combination of high dual infection rates and increased individual transmission risk demonstrates that cases of syphilis represent a strikingly high risk for HIV transmission in the United States wherever syphilis persists, especially if the prevalence of syphilis were to increase.

This review indicates that a high proportion of persons with syphilis are at risk for transmitting both diseases through sexual contact. The median HIV seroprevalence in patients with syphilis was 15.7% for men and women together, 27.5% for men alone, and 12.4% for women alone. The discrepancy of HIV seroprevalence by gender may be related to baseline HIV seroprevalence. The median HIV seroprevalences in persons without syphilis reported in the reviewed articles was 4.5 and 2.7 for men and women, respectively (data not shown). The majority of the studies showed an increased likelihood of HIV seroprevalence in persons with syphilis compared to similar populations without syphilis. One study with a newly emerging heterosexual epidemic of HIV infection found that HIV was exclusively present in the population with genital ulcer diseases, including syphilis.15 The two studies that showed no disease overlap were in populations in which the HIV seroprevalence was extremely low or nonexistent. One of these studies noted HIV infection only in the non-syphilis population.31 This may be due to the low number of patients with syphilis identified (n = 19) and the low seroprevalence of HIV in this population (0.4% in the referent group). The second study that noted no HIV seroprevalence in patients with syphilis was an outbreak investigation in rural Texas.47 The outbreak took place in four counties that had no cases of HIV identified among child-bearing women as part of a separate surveillance project (CDC, unpublished data). In addition, in the Texas outbreak, fewer than 20% of the identified cases of syphilis underwent testing for HIV. Overall, this review indicates that persons with syphilis are at substantially higher likelihood to be HIV seropositive than persons without syphilis.

Certain populations traditionally associated with increased prevalence of HIV (MSM and IDU) show high HIV coinfection with syphilis. In this study, HIV seroprevalences ranged from 64.3% to 90% and 22.5% to 70.6% for MSM and IDU, respectively. While these numbers reflect the high baseline HIV seroprevalence in these populations (data not shown), they also demonstrate a significantly increased prevalence of HIV infection in individuals with syphilis as shown in Table 3. Although some of these studies may have selected individuals with greater HIV seroprevalence because of their sampling techniques (i.e., persons actively seeking medical care), at least one study recruited participants from the community.53 These investigators reported a lower baseline HIV seroprevalence in the referent group compared to other studies, but they found a large increase in seroprevalence in persons with syphilis. Despite variable baseline seroprevalence, MSM and IDU consistently show an increased HIV seroprevalence in individuals with syphilis.

Because background HIV seroprevalence varies considerably across the United States and between subpopulations (such as persons who attend public STD clinics), we also calculated odds ratios when data were available. This study demonstrates a median odds ratio of 4.5 for men and women together. While the baseline HIV seroprevalences varied, all studies that provided information by sex showed increased odds of being HIV seropositive in the presence of syphilis. The odds ratios for men alone and women alone were 8.5 and 3.3, respectively. The reasons for the higher odds ratios in men are unclear, and might be an artifact of the populations from which the studies were chosen, an inherent increased risk based on gender, or additional factors not accounted for in this review. Increased odds ratios were also demonstrated for MSM and IDU.

This paper is unable to make any conclusion regarding causality or temporality of infections with HIV and syphilis. The biologic mechanisms involved in transmission were not investigated nor were other significant behavioral or clinical factors. We were unable to provide age-adjusted prevalences, and this may be a significant factor in the degree of overlap between HIV and syphilis. This article attempts to summarize the degree of concomitant HIV infection in individuals with syphilis compared to that in persons without syphilis. Given the relatively low prevalence of syphilis in the United States, it is unlikely that prospective studies that will clearly define the factors involved in this association would be feasible. Several states with the highest syphilis rates are not represented in the studies included in this paper. These areas are predominantly in the Southeastern United States and likely represented by the data presented.

There has been an 84% decline in primary and secondary syphilis rates in the United States from 1990 to 1997.54 This likely corresponds to a sharp decrease in syphilis-related HIV transmission. Recent outbreaks of syphilis are particularly concerning for the potential impact on local HIV transmission.24,25 The prospect remains that if the rates of syphilis return to the levels observed in the 1980s, there would likely be a substantial increase in the rate of HIV transmission.

The finding of increased HIV seroprevalence in persons with syphilis has significant public health implications. The value of detecting and treating a case of infectious syphilis goes beyond the medical and public health considerations of syphilis alone. Rather, timely and appropriate management of such cases eliminates an important facilitating factor for HIV transmission. Moreover, this intervention is “self-targeting” to individuals who often engage in high risk behavior and who may interact routinely with persons in high risk sexual networks. In addition, these results suggest that HIV counseling and testing, as recommended for all syphilis patients,21,22 will identify a number of persons who are HIV positive, and should be emphasized as a standard of care for all persons with syphilis. These findings also reinforce the potential impact of the national effort to eliminate syphilis from the United States as one highly targeted component of HIV prevention in the United States.22,26

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1. Cohen MS. Sexually transmitted diseases enhance HIV transmission: no longer a hypothesis. Lancet 1998;351(suppl 111):5–7.
2. Figueroa JP, Brathwaite A, Morris J, et al. Rising HIV-1 prevalence among sexually transmitted disease clinic attenders in Jamaica: traumatic sex and genital ulcers as risk factor. J AIDS 1994;7(3):310–316.
3. Mertens TE, Hayes RJ, Smith RG. Epidemiological methods to study the interaction between HIV infection and other sexually transmitted diseases. AIDS 1990;4:57–65.
4. Rompalo AM, Shepherd M, Lawlor JP, et al. Definitions of genital ulcer disease and variation in risk for prevalent human immunodeficiency virus infection. Sex Transm Dis 1997;24(7):436–442.
5. Wasserheit JN. Epidemiological synergy: interrelationships between human immunodeficiency virus and other sexually transmitted diseases. Sex Transm Dis 1992;9:61–77.
6. Dyer JR, Eron JJ, Hoffman IF, et al. Association of CD4 cell depletion and elevated blood and seminal plasma human immunodeficiency virus type 1 (HIV-1) RNA concentrations with genital ulcer disease in HIV-1 infected men in Malawi. J Infect Dis 1998;177:224–227.
7. Hayes RJ, Schulz KF, Plummer FA. The cofactor effect of genital ulcers on the per-exposure risk of HIV transmission in sub-Saharan Africa. J Trop Med Hygiene 1995;98:1–8.
8. Levine WC, Pope V, Bhoomkar A, et al. Increase in endocervical CD4 lymphocytes among women with nonulcerative sexually transmitted diseases. J Infect Dis 1998;177:167–174.
9. Moss GB, Overbaugh J, Welch M, et al. Human immunodeficiency virus DNA in urethral secretions in men: association with gonococcal urethritis and CD4 cell depletion. J Infect Dis 1995;172:1469–1474.
10. Spinola SM, Orazi A, Arno JN, et al. Haemophilus ducreyi elicits a cutaneous infiltrate of CD4 cells during experimental human infection. J Infect Dis 1996;173:394–402.
11. Telzak EE. Chiasson MA, Bevier PJ, Stoneburner RL, Castro KG, Jaffe HW. HIV-1 seroconversion in patients with and without genital ulcer disease. Ann Intern Med 1993;119:1181–1186.
12. Cohen MS, Hoffman IF, Royce RA, et al. Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. Lancet 1997;349:1868–1873.
13. Schacker T, Ryncarz AJ, Goddard J, Diem K, Shaughnessy M, Corey L. Frequent recovery of HIV-1 from genital herpes simplex virus lesions in HIV-1-infected men. JAMA 1998;280:61–66.
14. Kreiss JK, Coombs R, Plummer F, et al. Isolation of human immunodeficiency virus from genital ulcers in Nairobi prostitutes. J Infect Dis 1989;160(3):380–384.
15. Mertz KJ, Weiss JB, Webb RM, et al. An investigation of genital ulcers in Jackson, Mississippi, with use of a multiplex polymerase chain reaction assay: high prevalence of chancroid and immunodeficiency virus infection. J Infect Dis 1998;178(4):1060–1066.
16. Plummer FA, Wainberg MA, Plourde P, et al. Detection of human immunodeficiency virus type 1 (HIV-1) in genital ulcer exudate of HIV-1-infected men by culture and gene amplification [letter]. J Infect Dis 1990;161:810–811.
17. van Vorhis WC, Barrett LK, Nasio JM, Plummer FA, Lukehart SA. Lesions of primary and secondary syphilis contain activated cytolytic T cells. Infect Immun 1996;64(3):1048–1050.
18. Theus SA, Harrich DA, Gaynor R, Radolf JD, Norgard MV. Treponema pallidum, lipoproteins, and synthetic lipoprotein analogues induce human immunodeficiency virus type 1 gene expression in monocytes via NF-kB activation. J Infect Dis 1998;177:941–950.
19. Grosskurth H, Mosha F, Todd J, et al. Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomized controlled trial. Lancet 1995;346:530–6.
20. Wawer MJ. The Rakai randomized, community-based trial of STD control for AIDS prevention: no effect on HIV incidence despite reductions in STDs. In: Conference Supplement of the 12th World AIDS Conference, Geneva Switzerland, June 28-July 3, 1998. [Abstract no. 12473].
21. Centers for Disease Control and Prevention. 1998 Guidelines for treatment of sexually transmitted diseases. MMWR Morb Mort Wkly Rep 1998;47(No. RR-1):1–116.
22. Centers for Disease Control and Prevention. HIV prevention through early detection and treatment of other sexually transmitted diseases-United States. MMWR Morb Mort Wkly Rep 1998;47(No. RR-12):1–24.
23. Division of STD Prevention. Sexually transmitted diseases surveillance, 1996. U.S. Department of Health and Human Services, Public Health Service, Atlanta: Center for Disease Control and Prevention, September, 1997.
24. Centers for Disease Control and Prevention. Outbreak of primary and secondary syphilis-Guilford County, North Carolina, 1996–1997. MMWR Morb Mort Wkly Rep 1998;47(49):1070–1073.
25. Centers for Disease Control and Prevention. Outbreak of primary and secondary syphilis-Baltimore City, Maryland, 1995. MMWR Morb Mort Wkly Rep 1996;45(8):166–169.
26. St. Louis ME, Wasserheit JN. Elimination of syphilis in the United States. Science 1998;281:353–354.
27. Ansell DA, Chyn T, Straus M, Cohen M, Sherer R. HIV and syphilis seroprevalence among clients with sexually transmitted diseases attending a walk-in clinic at Cook County Hospital. Sex Transm Dis 1994;24(2):93–96.
28. Bansal J, Constantine NT, Zhang X, et al. Multiple blood-borne and sexually transmitted infections in sexually transmitted disease clinic and hospital emergency room patient populations. Sex Transm Dis 1991;20(4):220–226.
29. Caplan ES, Preas ME, Kerns T, et al. Seroprevalence of human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and rapid plasma reagin in a trauma population. J Trauma 1995;39(3):533–537.
30. Chirgwin K, DeHovitz JA, Dillon S, McCormack WM. HIV infection, genital ulcer disease and crack cocaine use among patients attending a clinic for sexually transmitted diseases. Am J Public Health 1991;81(12):1576–1579.
31. Goldberg MA, Laycock KA, Kinard S, Wang H, Pepose JS. Poor correlation between reactive syphilis serology and human immunodeficiency virus testing among potential cornea donors. Am J Ophthalmol 1995;119(1):1–6.
32. Gourevitch MN, Hartel D, Schoenbaum EE, et al. A prospective study of syphilis and HIV infection among injection drug users receiving methadone in the Bronx, NY. Am J Public Health 1996;86(8):1112–1115.
33. Gourevitch MN, Selwyn PA, Davenny K, et al. Effects of HIV infection on the serologic manifestations and response to treatment of syphilis in intravenous drug users. Ann Intern Med 1993;37:836–840.
    34. Herrera GA, Lackritz EM, Janssen RS, et al. Serologic test for syphilis as a surrogate marker for human immunodeficiency virus infection among United States blood donors. Transfusion 1997;37:836–840.
    35. Hoegsberg B, Abulafia O, Seldis A, et al. Sexually transmitted diseases and human immunodeficiency virus infections among women with pelvic inflammatory disease. Am J Obstet Gynecol 1990;163:1135–1139.
    36. Hutchinson CM, Rompalo AM, Reichart CA, Hook EW. Characteristics of patients with syphilis attending Baltimore STD clinics. Arch Intern Med 1991;151:511–516.
    37. McCabe E, Jaffe LR, Diaz A. Human immunodeficiency virus seropositivity in adolescents with syphilis. Pediatrics 1993;92(5):695–698.
    38. Minkoff HL, McCalla S, Delke I, Stevens R, Salwen M, Feldman J. The relationship of cocaine use to syphilis and human immunodeficiency virus infections among inner city parturient women. Am J Obstet Gynecol 1990;163:521–526.
    39. Centers for Disease Control and Prevention. HIV infection, syphilis, and tuberculosis screening among migrant farm workers-Florida, 1992. MMWR Morb Mort Wkly Rep 1992;41(39):723–725.
    40. Centers for Disease Control and Prevention. HIV seroprevalence in migrant and seasonal farm workers-North Carolina, 1987. MMWR Morb Mort Wkly Rep 1988;37(34):517–519.
    41. Otten Jr MW, Zaidi AA, Peterman TA, Rolfs RT, Witte JJ. High rate of HIV seroconversion among patients attending urban sexually transmitted disease clinics, AIDS 1994;8:549–553.
    42. Quinn TC, Cannon RO, Glasser D, et al. The association of syphilis with risk of human immunodeficiency virus infection in patients attending sexually transmitted disease clinics. Arch Intern Med 1990;150:1297–1302.
    43. Quinn TC, Glasser D, Cannon RO, et al. Human immunodeficiency virus infection among patients attending clinics for sexually transmitted diseases. N Engl J Med 1988;318:197–203.
    44. Rolfs RT, Joesoef MR, Hendershot EF, et al. A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. N Engl J Med 1997;337(5):307–314.
    45. Schoenbach VJ, Landis SE, Weber DJ, Mittal M, Koch GG, Levine PH. HIV seroprevalence in sexually transmitted disease clients in a low-prevalence southern state. Ann Epidemiol 1993;3:281–288.
    46. Schoenbaum EE, Webber MP, Vermund S, Gayle H. HIV antibody in persons screened for syphilis: prevalence in a New York City emergency room and primary care clinics. Sex Transm Dis 1990;17(4):190–193.
    47. Schulte JM, Ramsey HA, Paffel JM, et al. Outbreaks of syphilis is rural Texas towns, 1991–1992. South Med J 1994;87(4):493–496.
    48. Smith PF, Mikl J, Truman BI, et al. HIV infection among women entering the New York State correctional system. Am J Public Health 1991;81(suppl):35–40.
    49. Sperling RS, Joyner M, Hassett J, Kee R, Wheatley P, Bauer C. HIV-1 seroprevalence in pregnant women testing positive on serologic screening for syphilis. Mt Sinai J Med 1992;59(1):67–68.
    50. Stamm WE, Handsfield HH, Rompalo AM, Ashley RL, Roberts PL, Corey L. The association between genital ulcer disease and acquisition of HIV infection in homosexual men. JAMA 1988;260(10):1429–1433.
    51. Torian LV, Weisfuse IB, Makki HA, Benson DA, DiCamillo LM, Toribio FE. Increasing HIV-1 seroprevalence associated with genital ulcer disease, New York City, 1990–1992. AIDS 1995;9(2):177–181.
    52. Weisfuse IB, Greenberg BL, Back SD, et al. HIV-1 infection among New York City inmates. AIDS 1991;5(9):1133–1138.
    53. Williams ML, Elwood WN, Weatherby NL, et al. An assessment of the risks of syphilis and HIV infection among a sample of not-intreatment drug users in Houston, Texas. AIDS Care 1996;8(6):671–682.
    54. Centers for Disease Control and Prevention. Primary and Secondary Syphilis-United States, 1997. MMWR Morb Mort Wkly Rep 1998;47(24):493–497.
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