Ethics of screening for asymptomatic herpes virus type 2 infection
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《英国医生杂志》
1 Department of Public Health and Clinical Medicine, Epidemiology, Ume? University, Sweden, 2 Department of Dermatology and Venereology, Sahlgrenska University Hospital, Gothenberg, Sweden, 3 Skaraborg Institute for Research and Development, Sk?vde, Sweden, 4 Department of Medical Ethics, Lund University, Sweden
Correspondence to: I Krantz, Skaraborgsinstitutet, Stationsgatan 12, SE-541 30 Sk?vde, Sweden ingela.krantz@skaraborg-institute.se
Commercial tests for herpes simplex virus are now widely available, and some experts have advocated screening. But can screening be ethical when false positive results occur, many infected people are asymptomatic, and no cure is available?
Introduction
The only practical way to identify people with asymptomatic HSV-2 infection is by serological tests. Discussion is ongoing about how far to extend testing for HSV and for which groups, mostly with arguments from a biomedical perspective.w2-w12 Routine screening of pregnant women has been advocated, especially in the United States,w4 but its cost effectiveness has been questioned.5 Screening of asymptomatic people presenting for treatment of a suspected sexually transmitted disease has also been suggested, although no evidence exists to guide practice.6
Immunofluorescent photomicrograph of herpes simplex virus type 2
Credit: DR CRAIG LYERLA/CDC
Proponents for HSV-2 serology testing argue that patients seeking care for a suspected sexually transmitted disease have a right to be tested. One of the strongest arguments against such opportunistic screening is the possible psychosocial and psychosexual effects on asymptomatic people of discovering they have a disease that is sexually transmissible, incurable, and life long.
Effectiveness of tests for screening
Respect for individual autonomy often makes discussions about interventions that are justified by concerns for public health difficult and non-productive. But the issue in this case is not simply an individual one. HSV infection may have consequences for partners and offspring—some of them serious and even lethal.
A comprehensive ethical model is needed which considers the concerns of both individuals and public health. We have devised a framework for identifying and analysing the ethical conflicts inherent in screening for HSV-2 in asymptomatic individuals.10 11 The model identifies the people involved, formulates the relevant ethical principles, and assesses and weighs the ethical benefits and costs. The ethical deliberations below are made within a Swedish context, where the estimated seroprevalence is 15-20% and most cases of sexually transmitted infections are treated at STD clinics.12 No screening is done for HSV-2. Medical staff cannot coerce patients attending clinics to take the test because it is not on the list of diseases requiring statutory notification. In principle, but not always in practice, patients have a free choice about whether to take the test and inform partners of the results after being given neutral information.
Affected groups and three relevant ethical principles
The first task is to identify those affected or considered to be so in the public debate. The most important groups are people suspected to have an STD, their partners, and their unborn children. We also have to consider the staff at the STD clinics, as they would have to explain to patients why testing is important and then counsel those who test positive. This requires considerable knowledge of the natural course of the disease and the possibilities, benefits, and costs of treatment. Also relevant are policy makers, who are responsible for national surveillance of STDs, the public health, and the general public (table 2). The principles of autonomy (or respect for a person), beneficence (including non-maleficence), and justice (both solidarity and non-discrimination) seem relevant here.13 14 A combination of the six groups of people considered with the three ethical principles above will result in a matrix table, a checklist with 18 points noted by the letters A to R (table 2).
Table 2 Matrix showing points for discussion regarding ethical benefits and costs to those involved in screening for herpes simplex virus
Autonomy
The patient—that is, the person suspected to have an STD—has a right to decide whether to be tested. The prerequisite for exercising this right is adequate information. The decision is relatively easy for patients with suspected herpetic lesions, when the test is used to confirm the diagnosis. The situation is much more complicated for asymptomatic people, for whom the implications of a positive or negative result are not straightforward.
The partners' situation is also complicated. Again, testing can help confirm a diagnosis suspected on clinical grounds. An asymptomatic partner, however, will have the same problem as the index patient in understanding all the implications of the outcome of serotesting.
Current tests will have an ethical benefit when they are used to corroborate a clinical diagnosis and for asymptomatic people who are aware of the intricacies and implications of the testing procedure. On the other hand, the ethical costs will be very high if asymptomatic people who are not informed adequately are screened when attending an STD clinic. A positive result could raise questions of infidelity without due cause.
Screening of asymptomatic pregnant women and their partners is fraught with the same interpretation problems as for patients and complicated by deliberations on probabilities of transmission and occurrence of neonatal herpes. Since the risk of neonatal herpes is low in communities with low seroprevalence of HSV-2 and the serological status of the mother is not a reliable indicator of whether neonatal herpes is going to occur, the ethical costs of antenatal screening are high and the benefits doubtful.
Doctors often claim that it is better to know if you are infected than not to know. The evidence base for HSV-2 is patchy, and knowledge among non-specialists is sometimes lacking.15 The prerequisite of adequate information for exercising the right of autonomy will mostly not be met, implying ethical costs of screening in asymptomatic people even without persuasion taking place.
Staff also have a right to autonomy.16 This implies a delicate balance between the individual's personal morality and professional ethical guidelines. In our opinion, staff have an obligation to answer any questions related to health care. But do they have a professional obligation to inform all patients? If the patient refuses information this does not imply any autonomy costs for the staff.
We do not know the preferences of policy makers or the opinion of the general public. We assume that if genital herpes was experienced as an emerging epidemic, policy bodies would exercise their autonomous rights to intervene—for example, by making it a notifiable disease, introducing partner notification, and compulsory screening. Such action would imply ethical costs for the individual but benefits for the general public.
Beneficence
What are the best consequences for someone attending an STD clinic or general practice? The answer depends on whether the disease screened for is treatable by cure or relief of non-recognised symptoms. Symptomatic genital herpes can be relieved by antiviral drugs. Thus, a correct diagnosis provides ethical benefits for patients with symptoms. For asymptomatic people the costs would predominate, especially if they experience stigma and anxiety without having a true infection.
Such costs and benefits would also affect the partners. The patients' decisions regarding their partners might be based on self interest rather than what is best for a partner. A positive test result and counselling could have the desirable effect of preventing transmission. If testing is limited to patients with HIV, the risk of stigmatisation is substantial, although such patients could benefit for therapeutic reasons.17
Testing would benefit babies if it could correctly predict a serious outcome. Unfortunately, this is not the case.
Staff at STD clinics are unaffected by issues of beneficence, and the ethical benefits of a low prevalence of genital herpes for policy makers and the general public is obvious. However, it is not clear whether the same benefits apply to a low seroprevalence of HSV-2. A primary infection during late pregnancy is associated with a higher risk of transmission during delivery, which means high risk of viral exposure of the infant and a possible caesarean section. Here society would benefit more if the primary infections were experienced in age groups before pregnancy usually takes place.
Justice
Patients experience no justice costs if they are offered the test independently of social or economic status and are informed in a way that respects the individual variation in understanding and preparedness to internalise and act on the information. Within a high risk population, appeals to solidarity, as a requirement for diminishing the transmission and thereby the suffering, would be a possible strategy. However, because of the difficulties of understanding the problems and implications of the tests, equity might be jeopardised if all patients do not have access to specialists in venereology.15
The partners have to carry an unjust burden of the disease if infected but also if they are falsely labelled as having the disease. Nevertheless, we believe that tracing and contacting the partners for testing implies some justice benefits.
The risk of neonatal herpes is extremely small, especially in low prevalence populations. Thus, screening pregnant women for the benefit of unborn children seems to imply neither costs nor benefits with reference to justice.
Staffs and policy makers have a professional obligation to prevent transmission and promote safe sexual behaviour. A non-coercive, non-judgmental policy reflects a moral commitment to the interests of the individual patient. Lifestyle would not justify routine screening of so called "risk groups" without individual consent after adequate information. The definition of adequate information will vary with people and circumstances.
Is screening justified?
w1-w17 and definitions of ethical principles are on bmj.com
We thank the seminar group in medical ethics, Lund, for helpful comments.
Contributors and sources: IK is a specialist in infectious diseases and professor in epidemiology and public health with an interest in the ethics of public health. G-BL, IK, and BMA are part of a herpes research network in western Sweden. TN is professor in medical ethics. IK and TN had the idea for this paper, and IK wrote the first draft. All authors contributed to the final version from their special fields of competence. The article is based on sources from the Pub Med and medical ethics research literature. They are all guarantors.
Competing interests: None declared.
References
Koutsky LA, Ashley RL, Holmes KK, et al. The frequency of unrecognized type 2 herpes simplex virus infection among women. Sex Transm Dis 1990;17(2): 90-4.
Smith JS, Robinson NJ. Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review. J Infect Dis 2002;186(suppl 1): 3-28.
Wald A, Zeh J, Selke S, Warren T, Ryncarz AJ, Ashley R, et al. Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons. N Engl J Med 2000;342: 844-50.
Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L. Effect of serological status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. JAMA 2003;289: 203-9
Rouse DW, Stringer JSA. An appraisal of screening for maternal type-specific herpes simplex virus antibodies to prevent neonatal herpes. Am J Obstet Gynecol 2000;183: 400-5.
Scoular A. Using the evidence base on genital herpes: optimising the use of diagnostic tests and information provision. Sex Transm Infect 2002;78: 160-5.
Ashley RL. Sorting out the new HSV type specific antibody tests. Sex Transm Infect 2001;77: 232-7.
Fleming DT, McQuillan GM, Johnson JR, Nahmias, Aral OS, Lee FK, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med 1997;337: 1105-11.
Roest RW, van der Meijden WI, van Dijk G, Groen J, Mulder PG, Verjans GM, et al. Prevalence and association between herpes simplex virus types 1 and 2-specific antibodies in attendees at a sexually transmitted disease clinic. Int J Epidemiol 2001;30: 580-8.
Nilstun T. Forskningsetik i v?rd och medicin. . 2nd ed. Lund: Studentlitteratur, 1994.
Francoeur RT. Biomedical ethics. A guide to decision making. Canada: J Wiley, 1983.
Persson K, M?nsson A, Jonsson E, Nordenfelt E. Decline of herpes simplex virus type 2 and Chlamydia trachomatis infections from 1970 to 1993 indicated by a similar change in antibody pattern. Scand J Infect Dis 1995;27: 195-9.
Gillon R. Medical ethics: four principles plus attention to scope. BMJ 1994;309: 184.
Beauchamp TL, Childress JF. Principles of biomedical ethics. Oxford: Oxford University Press, 2001.
Narouz N, Allan PS, Wade AH. Genital herpes: general practitioners' knowledge and opinions. Sex Transm Infect 2002;78: 198-200.
Tran?y KE. Medicinsk etik i v?r tid . Lund: Studentlitteratur, 1993.
Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect 1999;75: 3-17.
Corey L, Handsfield HH. Genital herpes and public health. Addressing a global problem. JAMA 2000;283: 791-4.
Johnson RE, Nahmias AJ, Magder LS, Lee FK, Brooks CA, Snowden CB. A seroepidemiologic survey of the prevalence of herpes simplex type 2 infection in the United States. N Engl J Med 1989;321: 7-12.(Ingela Krantz, professor1)
Correspondence to: I Krantz, Skaraborgsinstitutet, Stationsgatan 12, SE-541 30 Sk?vde, Sweden ingela.krantz@skaraborg-institute.se
Commercial tests for herpes simplex virus are now widely available, and some experts have advocated screening. But can screening be ethical when false positive results occur, many infected people are asymptomatic, and no cure is available?
Introduction
The only practical way to identify people with asymptomatic HSV-2 infection is by serological tests. Discussion is ongoing about how far to extend testing for HSV and for which groups, mostly with arguments from a biomedical perspective.w2-w12 Routine screening of pregnant women has been advocated, especially in the United States,w4 but its cost effectiveness has been questioned.5 Screening of asymptomatic people presenting for treatment of a suspected sexually transmitted disease has also been suggested, although no evidence exists to guide practice.6
Immunofluorescent photomicrograph of herpes simplex virus type 2
Credit: DR CRAIG LYERLA/CDC
Proponents for HSV-2 serology testing argue that patients seeking care for a suspected sexually transmitted disease have a right to be tested. One of the strongest arguments against such opportunistic screening is the possible psychosocial and psychosexual effects on asymptomatic people of discovering they have a disease that is sexually transmissible, incurable, and life long.
Effectiveness of tests for screening
Respect for individual autonomy often makes discussions about interventions that are justified by concerns for public health difficult and non-productive. But the issue in this case is not simply an individual one. HSV infection may have consequences for partners and offspring—some of them serious and even lethal.
A comprehensive ethical model is needed which considers the concerns of both individuals and public health. We have devised a framework for identifying and analysing the ethical conflicts inherent in screening for HSV-2 in asymptomatic individuals.10 11 The model identifies the people involved, formulates the relevant ethical principles, and assesses and weighs the ethical benefits and costs. The ethical deliberations below are made within a Swedish context, where the estimated seroprevalence is 15-20% and most cases of sexually transmitted infections are treated at STD clinics.12 No screening is done for HSV-2. Medical staff cannot coerce patients attending clinics to take the test because it is not on the list of diseases requiring statutory notification. In principle, but not always in practice, patients have a free choice about whether to take the test and inform partners of the results after being given neutral information.
Affected groups and three relevant ethical principles
The first task is to identify those affected or considered to be so in the public debate. The most important groups are people suspected to have an STD, their partners, and their unborn children. We also have to consider the staff at the STD clinics, as they would have to explain to patients why testing is important and then counsel those who test positive. This requires considerable knowledge of the natural course of the disease and the possibilities, benefits, and costs of treatment. Also relevant are policy makers, who are responsible for national surveillance of STDs, the public health, and the general public (table 2). The principles of autonomy (or respect for a person), beneficence (including non-maleficence), and justice (both solidarity and non-discrimination) seem relevant here.13 14 A combination of the six groups of people considered with the three ethical principles above will result in a matrix table, a checklist with 18 points noted by the letters A to R (table 2).
Table 2 Matrix showing points for discussion regarding ethical benefits and costs to those involved in screening for herpes simplex virus
Autonomy
The patient—that is, the person suspected to have an STD—has a right to decide whether to be tested. The prerequisite for exercising this right is adequate information. The decision is relatively easy for patients with suspected herpetic lesions, when the test is used to confirm the diagnosis. The situation is much more complicated for asymptomatic people, for whom the implications of a positive or negative result are not straightforward.
The partners' situation is also complicated. Again, testing can help confirm a diagnosis suspected on clinical grounds. An asymptomatic partner, however, will have the same problem as the index patient in understanding all the implications of the outcome of serotesting.
Current tests will have an ethical benefit when they are used to corroborate a clinical diagnosis and for asymptomatic people who are aware of the intricacies and implications of the testing procedure. On the other hand, the ethical costs will be very high if asymptomatic people who are not informed adequately are screened when attending an STD clinic. A positive result could raise questions of infidelity without due cause.
Screening of asymptomatic pregnant women and their partners is fraught with the same interpretation problems as for patients and complicated by deliberations on probabilities of transmission and occurrence of neonatal herpes. Since the risk of neonatal herpes is low in communities with low seroprevalence of HSV-2 and the serological status of the mother is not a reliable indicator of whether neonatal herpes is going to occur, the ethical costs of antenatal screening are high and the benefits doubtful.
Doctors often claim that it is better to know if you are infected than not to know. The evidence base for HSV-2 is patchy, and knowledge among non-specialists is sometimes lacking.15 The prerequisite of adequate information for exercising the right of autonomy will mostly not be met, implying ethical costs of screening in asymptomatic people even without persuasion taking place.
Staff also have a right to autonomy.16 This implies a delicate balance between the individual's personal morality and professional ethical guidelines. In our opinion, staff have an obligation to answer any questions related to health care. But do they have a professional obligation to inform all patients? If the patient refuses information this does not imply any autonomy costs for the staff.
We do not know the preferences of policy makers or the opinion of the general public. We assume that if genital herpes was experienced as an emerging epidemic, policy bodies would exercise their autonomous rights to intervene—for example, by making it a notifiable disease, introducing partner notification, and compulsory screening. Such action would imply ethical costs for the individual but benefits for the general public.
Beneficence
What are the best consequences for someone attending an STD clinic or general practice? The answer depends on whether the disease screened for is treatable by cure or relief of non-recognised symptoms. Symptomatic genital herpes can be relieved by antiviral drugs. Thus, a correct diagnosis provides ethical benefits for patients with symptoms. For asymptomatic people the costs would predominate, especially if they experience stigma and anxiety without having a true infection.
Such costs and benefits would also affect the partners. The patients' decisions regarding their partners might be based on self interest rather than what is best for a partner. A positive test result and counselling could have the desirable effect of preventing transmission. If testing is limited to patients with HIV, the risk of stigmatisation is substantial, although such patients could benefit for therapeutic reasons.17
Testing would benefit babies if it could correctly predict a serious outcome. Unfortunately, this is not the case.
Staff at STD clinics are unaffected by issues of beneficence, and the ethical benefits of a low prevalence of genital herpes for policy makers and the general public is obvious. However, it is not clear whether the same benefits apply to a low seroprevalence of HSV-2. A primary infection during late pregnancy is associated with a higher risk of transmission during delivery, which means high risk of viral exposure of the infant and a possible caesarean section. Here society would benefit more if the primary infections were experienced in age groups before pregnancy usually takes place.
Justice
Patients experience no justice costs if they are offered the test independently of social or economic status and are informed in a way that respects the individual variation in understanding and preparedness to internalise and act on the information. Within a high risk population, appeals to solidarity, as a requirement for diminishing the transmission and thereby the suffering, would be a possible strategy. However, because of the difficulties of understanding the problems and implications of the tests, equity might be jeopardised if all patients do not have access to specialists in venereology.15
The partners have to carry an unjust burden of the disease if infected but also if they are falsely labelled as having the disease. Nevertheless, we believe that tracing and contacting the partners for testing implies some justice benefits.
The risk of neonatal herpes is extremely small, especially in low prevalence populations. Thus, screening pregnant women for the benefit of unborn children seems to imply neither costs nor benefits with reference to justice.
Staffs and policy makers have a professional obligation to prevent transmission and promote safe sexual behaviour. A non-coercive, non-judgmental policy reflects a moral commitment to the interests of the individual patient. Lifestyle would not justify routine screening of so called "risk groups" without individual consent after adequate information. The definition of adequate information will vary with people and circumstances.
Is screening justified?
w1-w17 and definitions of ethical principles are on bmj.com
We thank the seminar group in medical ethics, Lund, for helpful comments.
Contributors and sources: IK is a specialist in infectious diseases and professor in epidemiology and public health with an interest in the ethics of public health. G-BL, IK, and BMA are part of a herpes research network in western Sweden. TN is professor in medical ethics. IK and TN had the idea for this paper, and IK wrote the first draft. All authors contributed to the final version from their special fields of competence. The article is based on sources from the Pub Med and medical ethics research literature. They are all guarantors.
Competing interests: None declared.
References
Koutsky LA, Ashley RL, Holmes KK, et al. The frequency of unrecognized type 2 herpes simplex virus infection among women. Sex Transm Dis 1990;17(2): 90-4.
Smith JS, Robinson NJ. Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review. J Infect Dis 2002;186(suppl 1): 3-28.
Wald A, Zeh J, Selke S, Warren T, Ryncarz AJ, Ashley R, et al. Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons. N Engl J Med 2000;342: 844-50.
Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L. Effect of serological status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. JAMA 2003;289: 203-9
Rouse DW, Stringer JSA. An appraisal of screening for maternal type-specific herpes simplex virus antibodies to prevent neonatal herpes. Am J Obstet Gynecol 2000;183: 400-5.
Scoular A. Using the evidence base on genital herpes: optimising the use of diagnostic tests and information provision. Sex Transm Infect 2002;78: 160-5.
Ashley RL. Sorting out the new HSV type specific antibody tests. Sex Transm Infect 2001;77: 232-7.
Fleming DT, McQuillan GM, Johnson JR, Nahmias, Aral OS, Lee FK, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med 1997;337: 1105-11.
Roest RW, van der Meijden WI, van Dijk G, Groen J, Mulder PG, Verjans GM, et al. Prevalence and association between herpes simplex virus types 1 and 2-specific antibodies in attendees at a sexually transmitted disease clinic. Int J Epidemiol 2001;30: 580-8.
Nilstun T. Forskningsetik i v?rd och medicin. . 2nd ed. Lund: Studentlitteratur, 1994.
Francoeur RT. Biomedical ethics. A guide to decision making. Canada: J Wiley, 1983.
Persson K, M?nsson A, Jonsson E, Nordenfelt E. Decline of herpes simplex virus type 2 and Chlamydia trachomatis infections from 1970 to 1993 indicated by a similar change in antibody pattern. Scand J Infect Dis 1995;27: 195-9.
Gillon R. Medical ethics: four principles plus attention to scope. BMJ 1994;309: 184.
Beauchamp TL, Childress JF. Principles of biomedical ethics. Oxford: Oxford University Press, 2001.
Narouz N, Allan PS, Wade AH. Genital herpes: general practitioners' knowledge and opinions. Sex Transm Infect 2002;78: 198-200.
Tran?y KE. Medicinsk etik i v?r tid . Lund: Studentlitteratur, 1993.
Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect 1999;75: 3-17.
Corey L, Handsfield HH. Genital herpes and public health. Addressing a global problem. JAMA 2000;283: 791-4.
Johnson RE, Nahmias AJ, Magder LS, Lee FK, Brooks CA, Snowden CB. A seroepidemiologic survey of the prevalence of herpes simplex type 2 infection in the United States. N Engl J Med 1989;321: 7-12.(Ingela Krantz, professor1)