Cathy W. Critchlow

A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection.

Abstract Background. Human papillomavirus (HPV) has been associated with cervical intraepithelial neoplasia, but the temporal relation between the infection and the neoplasia remains unclear, as does the relative importance of the specific type of HPV, other sexually transmitted diseases, and other risk factors. Methods. We studied prospectively a cohort of 241 women who presented for evaluation of sexually transmitted disease and had negative cervical cytologic tests. The women were followed every four months with cytologic and colposcopic examinations of the uterine cervix and tests for HPV DNA and other sexually transmitted diseases. Results. Cervical intraepithelial neoplasia grade 2 or 3 was confirmed by biopsy in 28 women. On the basis of survival analysis, the cumulative incidence of cervical intraepithelial neoplasia at two years was 28 percent among women with a positive test for HPV and 3 percent among those without detectable HPV DNA. The risk was highest among those with HPV type 16 or 18 infe...

Diagnosis and clinical manifestations of bacterial vaginosis

Among 640 randomly selected women who were attending a sexually transmitted disease clinic and did not have trichomoniasis, 33% had bacterial vaginosis as defined by a composite of four clinical criteria: (1) Vaginal discharge was homogeneous; (2) vaginal discharge had a pH greater than or equal to 4.7; (3) vaginal discharge had an amine-like odor when mixed with 10% potassium hydroxide; (4) vaginal discharge contained clue cells representing greater than or equal to 20% of vaginal epithelial cells. Previously published Gram stain criteria for bacterial vaginosis correlated better than results of semiquantitative cultures for Gardnerella vaginalis with presence or absence of clue cells and with composite clinical criteria. Of 293 women with bacterial vaginosis by Gram stain criteria, 65% had symptoms of increased vaginal discharge and/or vaginal malodor, while 74% had signs of characteristic homogeneous vaginal discharge or amine-like odor. Elevated vaginal pH was the least specific and amine-like odor the least sensitive sign of bacterial vaginosis. Gram stain criteria for bacterial vaginosis were not associated with the concentrations of endocervical or vaginal inflammatory cells but were significantly associated with a clinical diagnosis of pelvic inflammatory disease. After adjusting for coinfection, sexual behavior, and other variables, bacterial vaginosis remained associated with adnexal tenderness (odds ratio = 9.2, p = 0.04). Bacterial vaginosis, previously implicated as a risk factor for obstetric infections, may be a risk factor for pelvic inflammatory disease.

Invasion of the Central Nervous System by Treponema pallidum: Implications for Diagnosis and Treatment

STUDY OBJECTIVES To determine the prevalence of Treponema pallidum in cerebrospinal fluid (CSF) of patients with syphilis, to determine the effect of concurrent HIV infection on central nervous system involvement by T. pallidum, and to examine the efficacy of conventional therapy for asymptomatic neurologic involvement. PATIENTS Fifty-eight patients with untreated syphilis who consented to lumbar puncture, representing approximately 10% of new cases of syphilis during the study period. INTERVENTIONS Lumbar puncture was done on all patients. Rabbit inoculation was used to test cerebrospinal fluid for viable T. pallidum. Patients with normal fluid received recommended benzathine penicillin therapy according to the stage of syphilis; patients with CSF abnormalities were offered 10-day therapy for neurosyphilis. RESULTS Treponema pallidum was isolated from the CSF of 12 (30%) of 40 patients (95% CI, 17 to 46) with untreated primary and secondary syphilis; isolation of T. pallidum was significantly associated (P = 0.008) with the presence of two or more abnormal laboratory variables (among leukocyte count, protein concentration, and CSF-Venereal Disease Research Laboratory [VDRL] test). Two (67%) of 3 early latent (CI, 13 to 100) and 3 (20%) of 15 late latent syphilis patients (CI, 5 to 47) also had reactive CSF-VDRL tests and elevated cell and protein levels, although T. pallidum was not isolated. Concurrent infection with the human immunodeficiency virus (HIV) was not associated with isolation of T. pallidum, increased number of CSF abnormalities, or reactive CSF serologic tests for syphilis, although CSF pleocytosis was commoner in subjects infected with HIV. Treatment with conventional benzathine penicillin G (2.4 mIU) failed to cure 3 of 4 patients with secondary syphilis from whom T. pallidum was isolated before therapy; all 3 patients in whom treatment failed were HIV seropositive when treated or seroconverted during follow-up. CONCLUSIONS Central nervous system invasion by T. pallidum is common in early syphilis, and is apparently independent of HIV infection. Examination of the CSF may be beneficial in patients with early syphilis, and therapy should be guided by knowledge of central nervous system involvement. Conventional benzathine penicillin G therapy may have reduced efficacy in patients with early syphilis who are also infected with HIV.

Genital ulceration as a risk factor for human immunodeficiency virus infection

Among 115 heterosexual men who presented with genital ulcers to a sexually transmitted disease clinic in Nairobi, Kenya, the prevalence of serum antibody to HIV was 16.5%. A past history of genital ulcers was reported by 12 (63%) of 19 men with antibody to HIV versus 30 (31%) of 96 without antibody (P = 0.008). HIV infection was also positively associated with lack of circumcision, but was not associated with the etiology of the current genital ulcer. Logistic regression analysis (adjusted for age, number of recent sex partners, recent prostitute contact, circumcision, tribal ethnic identity, past history of urethritis, and current diagnoses) confirmed only the association between prior history of genital ulcer disease and HIV infection; (P = 0.04, odds ratio 2.35, 95% confidence limits, 1.01-5.47). The incidence of genital ulcers, particularly chancroid, is much higher in parts of Africa than in Europe or North America. This may contribute to the increased risk of heterosexual transmission of HIV in Africa. Aggressive control of chancroid and syphilis may offer one very feasible approach to reducing transmission of HIV in this region.

Recurrences after oral and genital herpes simplex virus infection. Influence of site of infection and viral type

We prospectively followed 39 adults with concurrent primary herpes simplex virus (HSV) infection (12 with HSV type 1 and 27 with HSV type 2) of the oropharynx and genitalia, caused by the same virus in each person, to evaluate the influence of viral type (HSV-1 vs. HSV-2) and site of infection (oropharyngeal vs. genital) on the frequency of recurrence. The subsequent recurrence patterns of HSV infection differed markedly according to viral type and anatomical site. Oral-labial recurrences developed in 5 of 12 patients with HSV-1 and 1 of 27 patients with HSV-2 (P less than 0.001). Conversely, genital recurrences developed in 24 of 27 patients with HSV-2 and 3 of 12 patients with HSV-1 (P less than 0.01). The mean rate of subsequent genital recurrences (due to HSV-1 and HSV-2) was 0.23 per month, whereas the mean rate of oral-labial recurrences was only 0.04 per month (P less than 0.001). The mean monthly frequencies of recurrence were, in order, genital HSV-2 infections, 0.33 per month; oral-labial HSV-1 infections, 0.12 per month; genital HSV-1 infections, 0.020 per month; and oral HSV-2 infections, 0.001 per month (P less than 0.01 for each comparison). We conclude that the likelihood of reactivation of HSV infection differs between HSV-1 and HSV-2 infections and between the sacral and trigeminal anatomical sites. The sixfold more frequent clinical recurrence rate of genital HSV infections as compared with oral-labial HSV infections may account for the relatively rapid increase in the prevalence of clinically recognized genital herpes in recent years.

A Double-Blind Study of Oral Acyclovir for Suppression of Recurrences of Genital Herpes Simplex Virus Infection

Patients with frequently recurring genital herpes were enrolled in a double-blind placebo-controlled trial comparing 200-mg acyclovir capsules, given five or two times daily, with placebo. Of 47 placebo recipients, 44 (94 per cent) had recurrences during the 120-day treatment period, compared with 13 (29 per cent) of 45 patients treated with acyclovir five times daily and 18 of 51 (35 per cent) treated with acyclovir twice daily (P less than 0.001 for each regimen compared with placebo). The median time to the first clinical recurrence was 18 days in placebo recipients, compared with over 120 days in both acyclovir-treated groups (P less than 0.001 for both groups compared with placebo). The mean monthly recurrence rate during the medication period was 0.86 in placebo recipients, compared with 0.13 in patients treated with acyclovir five times daily and 0.14 in patients treated with acyclovir twice daily (P less than 0.001 for both groups compared with placebo). While receiving therapy, 86 of 96 acyclovir-treated patients had over a 50 per cent reduction in their pretreatment recurrence rate. Breakthrough recurrences in acyclovir recipients were of shorter duration and associated with a lower frequency of viral shedding than recurrences in placebo recipients. After medication was discontinued, the subsequent recurrence rate returned to pretreatment frequencies. Daily oral acyclovir was well tolerated. We conclude that oral acyclovir given for four months markedly reduces but does not completely prevent recurrences of genital herpes and does not influence the long-term natural history of the disease.

Mucopurulent cervicitis--the ignored counterpart in women of urethritis in men.

Among 100 randomly selected nonmenstruating women attending a clinic for sexually transmitted diseases, we assessed objective criteria for the clinical diagnosis of mucopurulent cervicitis. Visualization of yellow mucopurulent endocervical secretions on a white swab and the presence of 10 or more polymorphonuclear leukocytes per microscopical field (at a magnification of 1000) in satisfactory gram-stained endocervical smears were independently correlated with cervical Chlamydia trachomatis infection. Neither finding correlated with gonorrhea or genital herpes, although herpes caused characteristic cervical ulcerations. C. trachomatis was isolated from the cervix of 20 of 40 women with mucopurulent cervicitis but of only 2 of 60 without it. The overall prevalence of mucopurulent cervicitis among women attending the clinic (40 per cent) exceeded that of nongonococcal urethritis among men in the same clinic, and the prevalence of C. trachomatis infection was higher in mucopurulent cervicitis than in nongonococcal urethritis, a condition that is conventionally treated with tetracyclines. These findings support recommendations for the treatment of mucopurulent cervicitis and should guide the selective use of confirmatory diagnostic tests for C. trachomatis infection.

Mucopurulent Cervicitis and Mycoplasma genitalium

Many cases of mucopurulent cervicitis (MPC) are idiopathic and cannot be attributed to the known cervical pathogens Neisseria gonorrhoeae, Chlamydia trachomatis, or herpes simplex virus. Because Mycoplasma genitalium is associated with nongonoccocal urethritis in men, its role in MPC, the corresponding syndrome in women, was investigated. Archived cervical specimens from women recruited in the Harborview Sexually Transmitted Disease Clinic in Seattle from 1984 to 1986 were tested, using polymerase chain reaction, in a study that identified other causes of and risk factors for MPC. M. genitalium was detected in 50 (7.0%) of 719 women. Young age, multiple recent partners, prior miscarriage, smoking, menstrual cycle, and douching were positively associated with M. genitalium, whereas bacterial vaginosis and cunnilingus were negatively associated. After adjustment for age, phase of menstrual cycle, and presence of known cervical pathogens, women with M. genitalium had a 3.3-fold greater risk (95% confidence interval, 1.7-6.4) of MPC, which suggests that this organism may be a cause of MPC.

A Trial of Topical Acyclovir in Genital Herpes Simplex Virus Infections

Seventy-seven patients with first episodes of genital herpes and 111 with recurrent episodes were enrolled in a double-blind trial comparing topical acyclovir with a placebo (polyethylene glycol ointment). Among acyclovir-treated patients with first-episode primary genital herpes, the mean duration of viral shedding (4.1 days) and the time to complete crusting of lesions present at the initiation of therapy (7.1 days) were shorter than among placebo recipients (7.0 and 10.5 days, respectively) (P less than 0.05). Acyclovir-treated patients with recurrent herpes had a shorter duration of viral shedding than placebo recipients (0.95 vs. 1.90 days) (P = 0.03). Among the patients with recurrent herpes, acyclovir reduced the time to crusting of lesions in men but had no effect on the symptoms or healing times in women. Topical acyclovir shortens the duration of viral shedding and accelerates healing of some genital herpes simplex virus infections.

Effects on Infants of a First Episode of Genital Herpes during Pregnancy

Although genital herpes simplex virus (HSV) infections occurring during pregnancy are known to be associated with neonatal and maternal complications, their frequency and contributing risk factors are not well understood. We prospectively followed 29 patients who acquired genital herpes during pregnancy, to evaluate the perinatal effects of the infection. The patients were classified on the basis of clinical or serologic criteria. Fifteen patients had a primary first episode of genital HSV Type 2 (HSV-2), and 14 had a nonprimary first episode. Although no patient had disseminated disease, 6 of the 15 with primary genital herpes but none of 14 with nonprimary first-episode infection had infants with serious perinatal morbidity (P less than 0.01). Four of the five infants whose mothers acquired primary HSV-2 in the third trimester had perinatal morbidity such as prematurity, intrauterine growth retardation, and neonatal infection with HSV-2. Perinatal complications occurred in one of five infants whose mothers acquired primary HSV-2 during the first trimester, as well as in one of five infants whose mothers had primary HSV-2 during the second trimester. Asymptomatic cervical shedding of HSV-2 was detected at 10.6 percent of weekly visits made after a primary first episode, as compared with 0.5 percent of visits after a nonprimary first episode (P less than 0.01). We conclude that infants born to women who acquire primary genital herpes during pregnancy are at high risk of exposure to HSV, either during premature labor at the time of the primary episode or subsequently because of asymptomatic cervical shedding of the virus. The 40 percent incidence of serious perinatal morbidity in such women suggests that studies of preventive measures such as the use of antiviral chemotherapy are warranted.