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Changing patterns of genital herpes simplex virus infections
Zbl. Bakt. Hyg. A 268, 57-61 (1988)
Short Communication
Changing Patterns of Genital Herpes simplex Virus Infections STEVEN M. LIPSON l , KATARINA SZAB0 1,2, and JEN H. LIN l , 2 Virology Laboratory, Department of Pathology and Laboratories, Nassau County Medical Center , East Meadow , NY 11554 1 , and Department of Pathology, School of Medicine, State University of New York , Stony Brook, NY 11793 1,2
Received June 28, 1987 . Accepted September 14, 198 7
Abstract Herpes simplex virus type 2 is considered by many venereologists as the predominant serotype among those pati ents suffering from genital herpes. However, identification of genital isolates obtained from 16 through 20, and 31 through 40 year old individuals amon g our female patient population shows a predominance of HSV-l infections. Th ese dat a suggest that the "above the waist" - " below the waist" epidemiologic patterns commonly ascribed to reflect a prevalence of HSY-l and HSY-2 infections respectively, may no longer be appropriate in certain patient populations.
Zusammcnfassung Von vielen Venerologen wird der Typ 2 des Herpes simplex-Virus als der bei Patienten mit genitalem Herpes vorh errschende Serot yp angesehen. Die Identifizierung des Erregers bei Genitalisolaten weiblicher Patienten der Altersgruppen 16-20 und 31-40 Jahr e zeigte jedoch ein Vorherrschen von HSV-I-Infektionen. Diese Daten deuten darauf hin, daR die epidemiologischen Muster des Typs "uber der Taille " - " unter der Taille" , die, wie man ublicherweise annimmt, ein Vorh errschen von HSV-l- bzw. HSV-2-Infektionen widerspiegeln, vielleicht nicht mehr angebracht sind.
Introduction Typing of Herpes simplex virus (HSV) is performed at many large laboratories, as such data are important for prognostic purposes, in patient counseling, in epi demiologic studies, and perhaps in the choice of therapeutic modalities (1, 2, 3 ). HSV·l and HSV-2 have been broadly categorized according to the bod y site(s ) to which the se virus es att ack, and to their frequency of reacti vation (4, 5). However,
58
S.M. Lipson, K.Szabo, and J. H. Lin
British and American researchers reported high rates of HSV-l genital infections among female patients, thereby questioning the "above the waist" - "below the waist" dogma expounded by many medical personnel (6, 7, 8,9). The purpose of this study was to identify any disproportionate incidence of HSV-lI HSV-2 genital infections among our patient population, in order to determine any unique pattern in the natural history of these infections.
Materials and Methods During a 27 month period from July 1984 through November 1986, a total of 23,907 specimens (approximately 16,000 patients) receivedfor routine viral isolation, were screened for the presence of HSV. Six hundred fifty-one of 779 isolates (a 3.3% isolation rate) were categorized by type, source (i. e., genital, nongenital) of infection, patient age, and patient sex. Specimens were collected from throat, nasopharynx and rectum, and by rubbing/aspirating suspected genital vesicular lesions (i.e., patients clinically diagnosed as suffering from an HSV infection). Multiple genital specimens were rarely submitted. Isolation of the virus was performed in human embryonic kidney, with parallel inoculation of African Green monkey kidney (Vero) cell cultures. Infected cultures were transferred to slides, fixed in acetone, and stained to identify virus antigen by immunofluorescenceusing one and sometimes two sets of HSV type-specific monoclonal antibodies (10). The population tested represented broad socioeconomic levels, as specimens were received from various Nassau County Medical Center clinics, more than 13 hospitals, and approximately 30 physicians in private practice throughout Nassau, Suffolk, Queens, and Manhattan counties, New York, U.S.A.
Results and Discussion Forty-eight (55%) and 31 (46%) of 88 and 67 genital isolates obtained from 16 through 20 and 31 through 40 year old female patients were identified as HSV-l. A significantly lower percentage of type 1 genital herpes [37 (25%) of 148 isolates] were obtained from 21 through 30 year old patients (p < .001) (Tabler HSV-1, the predominant isolate obtained from nongenital specimens from both male and female children and teenagers (i. e. <: 15 years of age) is not unexpected, as serum antibodies to type 1 are commonly detected in prepuberty individuals. Dual (i. e., HSV-l and HSV-2) infections amount to approximately 0.4% (11), and consequently, have little effect on the interpretation of the ratios reported in this study. Most experts adhere to the classic above the waist-below the waist tenet characterizing the prevalence of HSV-l and HSV-2 infections, respectively (4, 5, 12). An exception to this epidemiologic pattern was ascribed to the occurrence of primary (i. e., no prior infection with HSV-l or HSV-2) genital infections, wherein HSV-l was most often identified. HSV-2 remained the most commonly identified among patients suffering from recurrent (i. e., positive HSV-2 serology) infections (2). Recurrent HSV-l infections were associated with nongenital sites. Several researchers have questioned whether primary or recurrent infections are truly associated with a prevalence of either HSV-l or HSV-2 genital infections, respectively. Smith et al. (13) for example, reported that HSY-2 infections occurred in 49 and 63 % of patients suffering from first episode external lesions and cervical ulcers, respec-
Changing Patterns of Genital Herpes simplex Virus Infections
59
Table 1. Identification of Herpes Simplex Virus isolates' Site of specimen Genital
Number of isolates 31-40 21-30
<: 15b
16-20
Vagina Labia Clitoris
4/l' 1/0 0/0
Vulva
111
14/7 9/11 0/0 25/22 d
10/35d 8/27d 0/0 19/4ge
3/7 4/10 1/0 13/19
3/3 0/4 0/3 6/11
Subtotal
6/2
48/40
37/111
31/36
9/30
Cervix Rectum Derus Perianal Other (oropharyngeal, face, finger, arm, buttock, leg, eye, ear)
0/0 1/0 0/0 0/0 35/2 d
6/15 1/0 1/0 5/2 32/2d
4/27 0/2 0/1 1/5 39/13 d
3/5 0/0 0/0 0/7 6/7
2/0 0/0 0/0 1/0 19/15
Subtotal
96/2
45/34
44/48
9/19
1/15
102/4
93/74
81/159
40/55
31/45
Total a b
c
d e
41
Herpes Simplex Virus type 2 predominated in all male genital isolates (data not shown) Patient age HSY-1/HSY-2 Dual isolate identified in one specimen Dual isolate identified in two specimens
tively. A second team of British researchers similarly reported that HSY isolates among 24 of 30 women suffering from primary infections, had no significant differences in the frequency of cervical involvement with either HSY-1 or HSY-2 (6). Corey and coworkers (14), showed an HSY-l isolation rate of only 7% (21 of 286) among patients reporting first episode genital herpes. Most recently, during a drug evaluation study, only 49% (33 of 67) of those patients suffering from first episode genital herpes were identified as sustaining a type 2 HSY infection (14a). In the 'current study, identification of HSY isolates showed a 55% genital HSY-1 isolation rate among 16-20 year old female patients, compared for example, to a 25% genital HSY-1 rate among 21-30 year old patients of the same sex. Although data comparing the prevalence of HSY-1 or HSY-2 to the incidence of primary or recurrent infections was unavailable (interviews could not be performed as our patient population was treated in other than STD c1inicals and by physicians in private practice), the significant difference in HSY type between the two age groups and the large population tested (> 5,000), suggests a changing pattern to the classic epidemiologically accepted appearance of the virus. It is difficult to explain the increased rate of genital HSY-l infections among some of our and the British patients studied. Perhaps these data reflect an increasing incidence of oral-genital contacts, autoinoculation, or a hormonally-induced selection against the replication of HSY-2 in the female genital tract (8, 15). In summary, our data (a) draw attention to significant differences in the incidence of HSY-l/HSY-2 genital infections among female patients of different age groups (b),
60
S.M. Lipson, K. Szabo, and]. H. Lin
further identifie s th e in decoro us association of HSV infections to body sites and (c), den ote the need of typi ng all HSV isolates, especially with the development and po ssible use of antivira l drugs differentially affecting the replication of one and not the other HSV type (16, 17, 18, 19 ).
Acknowledgment. The autho rs appreciate the excellent technical assista nce of P. Costello, R. Walderman, H. Middleton, R. Gulob, and C. Smith.
References
1. Rawls, W. E., A. Clark, K. O . Smith, J. j. Docherty, S. C. Gilman, and S. Graham: Cold Spring H arb or Conf. Cell Proliferation 7 (1980) 117-133 2. Reeves, W. c, L. Corey, H. G. Adams, L. A. Vontver, and K. K. Holmes: Risk of recurr ence after first episodes of genital herpes: relation to HSV type and antibody response. New Engl. ]. Med. 305 (1981) 315-3 19 3. Sacks, S. L.: Frequency and dur ation of patient-observed recurr ent genit al herpes simplex virus infectio n: cha racterization of the nonlesional syndrome. ] . infect. Dis. 150 (1984) 873-877 4. Corey, L. and P. G. Spear: Infections with herpes simplex viruses. (Second of two part s). New Engl. J. Med. 314 (1986) 749- 757 5. Drew, W. L. and W. E. Rawls: Herpes Simplex Viruses. In: E. H. Lennette, A. Baloiosm, W.]. Hauslerjr., and H. Jean Shadomy (eds.), Manual of Clinical M icrobi ology, 4th Edition (pp. 705-710). Amer. Soc. Microbiol., Washington DC (1985) 6. Barton, I. G., G. R. Kinghorn, S. Najem, L. S. AI-Omar, and C. W. Potter: The incidence of HSV-1 and HSV-2 isolated from a group of pat ients with herp es genita lis in Sheffield. Br.]. Vener. Dis. 58 (1982) 44-47 7. Kalinyak, J. E., G. Fleagle, and J. ]. Docherty: Incidence and distribution of herpes simplex virus-I and -2 from genital lesions in college women . ] . Med . Virol 1 (1979 ) 175-1 81 8. McCaughty, M. L., G. S. Fleagle, and J.]. Docherty: Inapparent genital herpes simplex virus infections in college women. J. Med. Virol. 10 (1982) 283-290. 9. Peutherer, J. F., I. W. Smith, and D. H. H. Robertson: Association of herp es simplex virus type 1 and 2 with clinical sites of infection. In: A. J. Nahamias, A. J. Dowdle, and R. F. Schinazi (eds.), The Hum an Herpesviruses, p. 595. Elsevier, New York (198 1) 10. Lipson, S. M., 1'. Schutzbank, and K. Szabo: Evaluation of three immunofluorescence assays for the culture confirm ation and typing of herpes simplex virus. ] . Clin. MicrobioI. 25 (1987) 391-394 11. Dragauan, j. , E. Patterson, R. Ashley, W. Lafferty, and L. Corey: Rout ine typing of herpes simplex virus isolates. Diag. Microbiol. Infect. Dis. 3 (1985) 269-271 12. Becker, T. M. and A. ]. Nahamias: Genital herpes - Yesterda y, tod ay, and tomorrow. Ann. Rev. Med. 36 (1985) 185- 193 13. Smith, I. W., ]. F. Peutherer, and j. M. Hunter: Cervical infection with herpes simplex virus. Lan cet i (1981) 1051 14. Corey, L., H. G. Adams, Z. A. Brown, and K. K. Holmes: Genital herpes simplex virus infection: Clinical manifestations, course, and complications. Ann. Intern . Med. 98 (1983) 958-972 14a. Mindel, A., E. Allason-Jones, I. Barton, M. Jeavons, G. Kinghorn, P. Woolley, A. Faherty, P. Williams, and G. Patou: Treatment of first-attack genital herp es acyclovir versus inosine pr anobex. Lancet i (1987) 171-173 15. Newcomer, S. F. and ]. R. Udry: Ora l sex in an adolescent popul ation. Arch. Sex Behav. 14 (1985) 41-46
Changing Patterns of Genital Herpes simplex Virus Infections
61
16. Collins, P. and D. ]. Bauer: Relative potency of anti-herpes compounds. Ann. N.Y. Acad. Sci. 284 (1977) 49-59
17. Crumpacker, C. S., 1. E. Schnipper, ]. A. Zaia, and M. ]. Levin: Growth inhibition by acycloguanosine of herpesviruses isolated from human infections. Antimicrob, Agents Chemother 15 (1976) 642-645 18. DeClercq, E.,]. Descamps, G. Verheist, R. T. Walker, A. S. Jones, P. F. Torrence, and D. Shugar: Comparative sensitivity of antiherpes drugs against different strains of herpes simplex virus.]. infect. Dis. 141 (1980) 563-574 19. Teh, Ci-Z. and S. 1. Sacks: Susceptibility of recent clinical isolates of Herpes Simplex Virus to 5-ethyl-2' deoxyuridine: preferential inhibition of Herpes Simplex Virus type 2. 1983. Antimicrob. Agents Chemother. 23 (1983) 637-640 Dr. Steven M. Lipson, Virology Laboratory, Division of Microbiology, Department of Pathology and Laboratories, Nassau County Medical Center, 2201 Hempstead Turnpike, East Meadow, NY 11554, U.S.A.
Short Communication
Changing Patterns of Genital Herpes simplex Virus Infections STEVEN M. LIPSON l , KATARINA SZAB0 1,2, and JEN H. LIN l , 2 Virology Laboratory, Department of Pathology and Laboratories, Nassau County Medical Center , East Meadow , NY 11554 1 , and Department of Pathology, School of Medicine, State University of New York , Stony Brook, NY 11793 1,2
Received June 28, 1987 . Accepted September 14, 198 7
Abstract Herpes simplex virus type 2 is considered by many venereologists as the predominant serotype among those pati ents suffering from genital herpes. However, identification of genital isolates obtained from 16 through 20, and 31 through 40 year old individuals amon g our female patient population shows a predominance of HSV-l infections. Th ese dat a suggest that the "above the waist" - " below the waist" epidemiologic patterns commonly ascribed to reflect a prevalence of HSY-l and HSY-2 infections respectively, may no longer be appropriate in certain patient populations.
Zusammcnfassung Von vielen Venerologen wird der Typ 2 des Herpes simplex-Virus als der bei Patienten mit genitalem Herpes vorh errschende Serot yp angesehen. Die Identifizierung des Erregers bei Genitalisolaten weiblicher Patienten der Altersgruppen 16-20 und 31-40 Jahr e zeigte jedoch ein Vorherrschen von HSV-I-Infektionen. Diese Daten deuten darauf hin, daR die epidemiologischen Muster des Typs "uber der Taille " - " unter der Taille" , die, wie man ublicherweise annimmt, ein Vorh errschen von HSV-l- bzw. HSV-2-Infektionen widerspiegeln, vielleicht nicht mehr angebracht sind.
Introduction Typing of Herpes simplex virus (HSV) is performed at many large laboratories, as such data are important for prognostic purposes, in patient counseling, in epi demiologic studies, and perhaps in the choice of therapeutic modalities (1, 2, 3 ). HSV·l and HSV-2 have been broadly categorized according to the bod y site(s ) to which the se virus es att ack, and to their frequency of reacti vation (4, 5). However,
58
S.M. Lipson, K.Szabo, and J. H. Lin
British and American researchers reported high rates of HSV-l genital infections among female patients, thereby questioning the "above the waist" - "below the waist" dogma expounded by many medical personnel (6, 7, 8,9). The purpose of this study was to identify any disproportionate incidence of HSV-lI HSV-2 genital infections among our patient population, in order to determine any unique pattern in the natural history of these infections.
Materials and Methods During a 27 month period from July 1984 through November 1986, a total of 23,907 specimens (approximately 16,000 patients) receivedfor routine viral isolation, were screened for the presence of HSV. Six hundred fifty-one of 779 isolates (a 3.3% isolation rate) were categorized by type, source (i. e., genital, nongenital) of infection, patient age, and patient sex. Specimens were collected from throat, nasopharynx and rectum, and by rubbing/aspirating suspected genital vesicular lesions (i.e., patients clinically diagnosed as suffering from an HSV infection). Multiple genital specimens were rarely submitted. Isolation of the virus was performed in human embryonic kidney, with parallel inoculation of African Green monkey kidney (Vero) cell cultures. Infected cultures were transferred to slides, fixed in acetone, and stained to identify virus antigen by immunofluorescenceusing one and sometimes two sets of HSV type-specific monoclonal antibodies (10). The population tested represented broad socioeconomic levels, as specimens were received from various Nassau County Medical Center clinics, more than 13 hospitals, and approximately 30 physicians in private practice throughout Nassau, Suffolk, Queens, and Manhattan counties, New York, U.S.A.
Results and Discussion Forty-eight (55%) and 31 (46%) of 88 and 67 genital isolates obtained from 16 through 20 and 31 through 40 year old female patients were identified as HSV-l. A significantly lower percentage of type 1 genital herpes [37 (25%) of 148 isolates] were obtained from 21 through 30 year old patients (p < .001) (Tabler HSV-1, the predominant isolate obtained from nongenital specimens from both male and female children and teenagers (i. e. <: 15 years of age) is not unexpected, as serum antibodies to type 1 are commonly detected in prepuberty individuals. Dual (i. e., HSV-l and HSV-2) infections amount to approximately 0.4% (11), and consequently, have little effect on the interpretation of the ratios reported in this study. Most experts adhere to the classic above the waist-below the waist tenet characterizing the prevalence of HSV-l and HSV-2 infections, respectively (4, 5, 12). An exception to this epidemiologic pattern was ascribed to the occurrence of primary (i. e., no prior infection with HSV-l or HSV-2) genital infections, wherein HSV-l was most often identified. HSV-2 remained the most commonly identified among patients suffering from recurrent (i. e., positive HSV-2 serology) infections (2). Recurrent HSV-l infections were associated with nongenital sites. Several researchers have questioned whether primary or recurrent infections are truly associated with a prevalence of either HSV-l or HSV-2 genital infections, respectively. Smith et al. (13) for example, reported that HSY-2 infections occurred in 49 and 63 % of patients suffering from first episode external lesions and cervical ulcers, respec-
Changing Patterns of Genital Herpes simplex Virus Infections
59
Table 1. Identification of Herpes Simplex Virus isolates' Site of specimen Genital
Number of isolates 31-40 21-30
<: 15b
16-20
Vagina Labia Clitoris
4/l' 1/0 0/0
Vulva
111
14/7 9/11 0/0 25/22 d
10/35d 8/27d 0/0 19/4ge
3/7 4/10 1/0 13/19
3/3 0/4 0/3 6/11
Subtotal
6/2
48/40
37/111
31/36
9/30
Cervix Rectum Derus Perianal Other (oropharyngeal, face, finger, arm, buttock, leg, eye, ear)
0/0 1/0 0/0 0/0 35/2 d
6/15 1/0 1/0 5/2 32/2d
4/27 0/2 0/1 1/5 39/13 d
3/5 0/0 0/0 0/7 6/7
2/0 0/0 0/0 1/0 19/15
Subtotal
96/2
45/34
44/48
9/19
1/15
102/4
93/74
81/159
40/55
31/45
Total a b
c
d e
41
Herpes Simplex Virus type 2 predominated in all male genital isolates (data not shown) Patient age HSY-1/HSY-2 Dual isolate identified in one specimen Dual isolate identified in two specimens
tively. A second team of British researchers similarly reported that HSY isolates among 24 of 30 women suffering from primary infections, had no significant differences in the frequency of cervical involvement with either HSY-1 or HSY-2 (6). Corey and coworkers (14), showed an HSY-l isolation rate of only 7% (21 of 286) among patients reporting first episode genital herpes. Most recently, during a drug evaluation study, only 49% (33 of 67) of those patients suffering from first episode genital herpes were identified as sustaining a type 2 HSY infection (14a). In the 'current study, identification of HSY isolates showed a 55% genital HSY-1 isolation rate among 16-20 year old female patients, compared for example, to a 25% genital HSY-1 rate among 21-30 year old patients of the same sex. Although data comparing the prevalence of HSY-1 or HSY-2 to the incidence of primary or recurrent infections was unavailable (interviews could not be performed as our patient population was treated in other than STD c1inicals and by physicians in private practice), the significant difference in HSY type between the two age groups and the large population tested (> 5,000), suggests a changing pattern to the classic epidemiologically accepted appearance of the virus. It is difficult to explain the increased rate of genital HSY-l infections among some of our and the British patients studied. Perhaps these data reflect an increasing incidence of oral-genital contacts, autoinoculation, or a hormonally-induced selection against the replication of HSY-2 in the female genital tract (8, 15). In summary, our data (a) draw attention to significant differences in the incidence of HSY-l/HSY-2 genital infections among female patients of different age groups (b),
60
S.M. Lipson, K. Szabo, and]. H. Lin
further identifie s th e in decoro us association of HSV infections to body sites and (c), den ote the need of typi ng all HSV isolates, especially with the development and po ssible use of antivira l drugs differentially affecting the replication of one and not the other HSV type (16, 17, 18, 19 ).
Acknowledgment. The autho rs appreciate the excellent technical assista nce of P. Costello, R. Walderman, H. Middleton, R. Gulob, and C. Smith.
References
1. Rawls, W. E., A. Clark, K. O . Smith, J. j. Docherty, S. C. Gilman, and S. Graham: Cold Spring H arb or Conf. Cell Proliferation 7 (1980) 117-133 2. Reeves, W. c, L. Corey, H. G. Adams, L. A. Vontver, and K. K. Holmes: Risk of recurr ence after first episodes of genital herpes: relation to HSV type and antibody response. New Engl. ]. Med. 305 (1981) 315-3 19 3. Sacks, S. L.: Frequency and dur ation of patient-observed recurr ent genit al herpes simplex virus infectio n: cha racterization of the nonlesional syndrome. ] . infect. Dis. 150 (1984) 873-877 4. Corey, L. and P. G. Spear: Infections with herpes simplex viruses. (Second of two part s). New Engl. J. Med. 314 (1986) 749- 757 5. Drew, W. L. and W. E. Rawls: Herpes Simplex Viruses. In: E. H. Lennette, A. Baloiosm, W.]. Hauslerjr., and H. Jean Shadomy (eds.), Manual of Clinical M icrobi ology, 4th Edition (pp. 705-710). Amer. Soc. Microbiol., Washington DC (1985) 6. Barton, I. G., G. R. Kinghorn, S. Najem, L. S. AI-Omar, and C. W. Potter: The incidence of HSV-1 and HSV-2 isolated from a group of pat ients with herp es genita lis in Sheffield. Br.]. Vener. Dis. 58 (1982) 44-47 7. Kalinyak, J. E., G. Fleagle, and J. ]. Docherty: Incidence and distribution of herpes simplex virus-I and -2 from genital lesions in college women . ] . Med . Virol 1 (1979 ) 175-1 81 8. McCaughty, M. L., G. S. Fleagle, and J.]. Docherty: Inapparent genital herpes simplex virus infections in college women. J. Med. Virol. 10 (1982) 283-290. 9. Peutherer, J. F., I. W. Smith, and D. H. H. Robertson: Association of herp es simplex virus type 1 and 2 with clinical sites of infection. In: A. J. Nahamias, A. J. Dowdle, and R. F. Schinazi (eds.), The Hum an Herpesviruses, p. 595. Elsevier, New York (198 1) 10. Lipson, S. M., 1'. Schutzbank, and K. Szabo: Evaluation of three immunofluorescence assays for the culture confirm ation and typing of herpes simplex virus. ] . Clin. MicrobioI. 25 (1987) 391-394 11. Dragauan, j. , E. Patterson, R. Ashley, W. Lafferty, and L. Corey: Rout ine typing of herpes simplex virus isolates. Diag. Microbiol. Infect. Dis. 3 (1985) 269-271 12. Becker, T. M. and A. ]. Nahamias: Genital herpes - Yesterda y, tod ay, and tomorrow. Ann. Rev. Med. 36 (1985) 185- 193 13. Smith, I. W., ]. F. Peutherer, and j. M. Hunter: Cervical infection with herpes simplex virus. Lan cet i (1981) 1051 14. Corey, L., H. G. Adams, Z. A. Brown, and K. K. Holmes: Genital herpes simplex virus infection: Clinical manifestations, course, and complications. Ann. Intern . Med. 98 (1983) 958-972 14a. Mindel, A., E. Allason-Jones, I. Barton, M. Jeavons, G. Kinghorn, P. Woolley, A. Faherty, P. Williams, and G. Patou: Treatment of first-attack genital herp es acyclovir versus inosine pr anobex. Lancet i (1987) 171-173 15. Newcomer, S. F. and ]. R. Udry: Ora l sex in an adolescent popul ation. Arch. Sex Behav. 14 (1985) 41-46
Changing Patterns of Genital Herpes simplex Virus Infections
61
16. Collins, P. and D. ]. Bauer: Relative potency of anti-herpes compounds. Ann. N.Y. Acad. Sci. 284 (1977) 49-59
17. Crumpacker, C. S., 1. E. Schnipper, ]. A. Zaia, and M. ]. Levin: Growth inhibition by acycloguanosine of herpesviruses isolated from human infections. Antimicrob, Agents Chemother 15 (1976) 642-645 18. DeClercq, E.,]. Descamps, G. Verheist, R. T. Walker, A. S. Jones, P. F. Torrence, and D. Shugar: Comparative sensitivity of antiherpes drugs against different strains of herpes simplex virus.]. infect. Dis. 141 (1980) 563-574 19. Teh, Ci-Z. and S. 1. Sacks: Susceptibility of recent clinical isolates of Herpes Simplex Virus to 5-ethyl-2' deoxyuridine: preferential inhibition of Herpes Simplex Virus type 2. 1983. Antimicrob. Agents Chemother. 23 (1983) 637-640 Dr. Steven M. Lipson, Virology Laboratory, Division of Microbiology, Department of Pathology and Laboratories, Nassau County Medical Center, 2201 Hempstead Turnpike, East Meadow, NY 11554, U.S.A.