Importancia de los exámenes serológicos en los pacientes con Herpes Simple I y II.
A Recommendation Against Serologic Screening for Genital Herpes Infection—What Now?
Genital herpes, one of the most prevalent sexually transmitted infections (STIs) in the United States, is caused either by herpes simplex virus (HSV) type 2 (HSV-2), a virus that almost exclusively causes genital infections, or increasingly by HSV type 1 (HSV-1), a closely related virus that causes both oro-labial herpes ("cold sores") and genital herpes.,2 Genital herpes should be prioritized as a public health problem. HSV-2 is estimated to infect more than 45 million individuals (15.3%) living in the United States aged 14 to 49 years, and more than 10% to 20% of new genital herpes infections are now caused by HSV-1. Further, genital herpes is an example of the striking health disparities that characterize STIs in the United States; HSV-2 seroprevalence among non-Hispanic blacks (about 39%) is far higher than the seroprevalence among whites (about 12%).,3 Congenital herpes, which is not a reportable condition, is estimated to be more than twice as common as congenital syphilis (31/100 000 vs 12.4/100 000 live births) and can be devastating for children born to infected mothers. In addition, there is a strong association between genital herpes infection and increased risk for acquisition of human immunodeficiency virus type 1.,5
There is no cure for genital herpes or a vaccine to prevent infection. Despite high rates and the considerable morbidity associated with genital herpes, at present there is no coordinated national effort to control genital herpes. Efforts to reduce genital herpes morbidity are challenging, because most infected persons are unaware of their infections yet remain at risk for transmission of infection to others.,3,6
A first step in confronting a widespread, largely underrecognized public health problem is to identify infected individuals to prevent further transmission. In this issue of JAMA, the US Preventive Services Task Force (USPSTF) presents an update of its 2005 recommendation and once again has recommended "against routine serologic screening for genital HSV infection in asymptomatic adolescents and adults, including those who are pregnant (D recommendation)." The task force noted problems of poor test performance, potential harms that might result from screening, and limited evidence of benefit from medical treatment to reduce transmission to uninfected sex partners or children born to infected mothers.
These recommendations are based on a comprehensive review of the literature, also published in this issue of JAMA, by Feltner and colleagues, who reviewed the accuracy, benefits, and harms of serologic screening for HSV-2 in asymptomatic persons, including pregnant women. The literature review also assessed the effectiveness of administration of preventive medication and counseling for reducing future symptomatic recurrences or transmission to uninfected persons. After consideration of the natural history of genital herpes, the epidemiology of infection, and available evidence on serologic screening for herpes, the USPSTF again concluded that the potential harms of serologic screening are greater than the benefits of serologic screening of otherwise asymptomatic adolescents and adults, including pregnant women.
A major problem identified by the review and leading to the recommendation against screening is unsatisfactory test performance. Feltner et al reviewed 11 evaluable studies, all conducted in populations with more than double the estimated US population prevalence of infection, and concluded that current tests are not suitable for use in the general, asymptomatic sexually active population. In these studies, using the manufacturer's cutpoint for interpretation of results, the sensitivity of the test most widely used for detection of serologic evidence of HSV-2 infection was high (99%), but the specificity was so low (83% [95% CI, 72%-90%]) that screening a population with an HSV-2 seroprevalence about the same as for US residents aged 14 to 49 years (16%) would yield nearly as many false-positive results as true infections. Using higher cutpoints for determining test positivity did not improve the performance sufficiently to provide confidence in the test results when used for general screening. These are not new findings. Despite well more than a decade of appreciation of suboptimal test performance as a tool for general population screening, commercially available tests have not evolved.
Clearly there is room for improvement of available tests as well as for development of new tests. In addition to development of better tests, a research agenda should evaluate the utility of routine implementation of a 2-step testing process in which specimens yielding an initial positive result are then tested using a second test targeting different HSV antigens for purposes of confirmation. Use of currently available tests in this way has been demonstrated to improve the specificity and predictive value somewhat, although not enough to allow this recommendation to be used in screening for the general population.,9 This approach, modeled after the "screen-confirm" model used for infections such as syphilis, should be further evaluated as a means of improving the performance of new and currently available tests in appropriate populations.
The recommendation against serologic screening for genital HSV is warranted but should concern clinicians and patients and serve as a call to action for the National Institutes of Health, other federal agencies, and industry partners to address this ongoing epidemic, prioritizing development of improved tests and test strategies for diagnosis of HSV.
In addition, these conclusions should foster vigorous campaigns that seek to reduce the pervasive stigma that affects individuals diagnosed with HSV and hinders management and control efforts. Throughout the 20th century, popular perceptions and much of public health STI prevention education has tended to foster stigmatization of persons who have acquired STIs. The potential harm described by Feltner et al is real and demonstrates the harm that can result from misinformation and misperception. Widespread misperceptions regarding the severity, lack of effective treatment, and physical morbidity of genital herpes contribute to disproportionate concerns about genital herpes infection and stigmatization of those infected. These misperceptions should serve as impetus for work to reduce the stigma associated with STIs, including herpes.
Public perception about the consequences and morbidity of genital herpes is not consistent with current knowledge of the natural history of infection and the experience of clinicians who regularly care for persons with infection. That more than 8 of 10 people who have genital herpes are unaware of their infection,6 serves to emphasize that this disorder is not always obvious to those infected or those who care for such persons and suggests that infected persons can live normal lives despite their infection. Randomized clinical trials have demonstrated that currently available therapy reduces the discomfort and duration of outbreaks and that chronic suppressive therapy reduces both recurrences and transmission to others. In addition, the randomized crossover clinical trial by Wald and colleaguesalso described in this issue of JAMA is an example of continuing progress in development of new antiviral agents for HSV management. In this study of 91 adults with frequently recurring genital HSV-2, daily oral pritelivir compared with oral valacyclovir reduced the percentage of genital swabs with detected HSV (an indicator of genital shedding) (2.4% vs 5.3%) and the percentage of days with genital lesions present (1.9% vs 3.9%). Although further research is needed to assess longer-term efficacy and safety, this study contributes to the research base that should inform current efforts to emphasize scientific evidence and sexual health over disease-related morbidity and should help address misperceptions about this common infection.
The recommendation from the USPSTF and the results of the accompanying evidence review should not be misinterpreted to assume that currently available tests, despite their limitations, do not have a role in some elements of current HSV management. Nor should these reports be interpreted to suggest that progress is not being made in expanding management options for treatment of genital herpes. Currently available tests, even with their suboptimal performance characteristics, remain useful for diagnostic testing and for evaluation of persons with histories of recurring anogenital lesions and provide information that may influence treatment decisions based on which virus type (HSV-1 or HSV-2) is present in persons with genital HSV. Current tests also provide important information for sex partners of persons diagnosed with HSV who are uncertain of their own status and for other suggestive but not definitive symptoms or signs.
While it is disappointing that so little progress in test performance has occurred in the more than a decade since the 2005 USPTF recommendation against general population screening for this important and widespread STI, the current USPSTF recommendation should serve to renew efforts to develop better tests for HSV, to improve management strategy, and to address the pervasive and harmful stigma associated with genital herpes.
Article Information
Corresponding Author: Edward W. Hook III, MD, Department of Microbiology, The University of Alabama at Birmingham, 703 19th St S, Zeigler Research Bldg 242, Birmingham, AL 35294-0006 (ehook@uab.edu).
Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and reported receiving grants from Hologic and Roche Molecular, a grant and personal fees from Becton Dickinson, and research supplies from Cepheid.
References
Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2015. Atlanta, GA: US Dept of Health and Human Services; 2016.
PubMed
PubMed
Brandt AM. No Magic Bullet: A Social History of Venereal Disease in the United States Since 1880. New York, NY: Oxford University Press; 1985.
Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted treatment guidelines, 2015 [published correction appears in MMWR Recomm Rep. 2015;64:33]. MMWR Morb Mortal Wkly Rep. 2015;64(RR-03):1-137.
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December 20, 2016
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