The etiology of genital ulcer disease by multiplex polymerase chain reaction and relationship to HIV infection among patients attending sexually transmitted disease clinics in Pune, India

Abstract

Objectives: To determine the etiology of genital ulcer disease (GUD) among patients attending sexually transmitted disease (STD) clinics in Pune, India, and to examine the relationship to HIV infection and compare the clinical diagnosis of GUD with the results of a multiplex polymerase chain reaction (M-PCR) assay for Treponema pallidum, herpes simplex virus (HSV), and Hemophilus ducreyi infection.

Methods: Between June 20, 1994, and September 26, 1994, 302 patients with a genital ulcer were evaluated. Clinical etiology of GUD was based on physical appearance and microbiologic evaluations which included darkfield microscopy and serology for syphilis. Swabs of each genital ulcer were tested for HSV antigen by enzyme immunoassay (Herpchek; Dupont, Wilmington, DE) and processed in a multiplex PCR assay (M-PCR; Roche, Branchburg, NJ) for simultaneous detection of HSV, Treponema pallidum, and Hemophilus ducreyi.

Results: Two hundred seventy-seven men and 25 women with a median age of 25 were evaluated. The seroprevalence of HIV was 22.2%. The etiology of GUD as determined by M-PCR was HSV (26%), H. ducreyi (23%), T. pallidum (10%), and multiple infections (7%); no etiology was identified in 34%. HIV seroprevalence was higher among those patients positive for HSV compared with other etiologies (OR = 2.1, CI: 1.2-3.7; p = 0.01). When compared with M-PCR, the Herpchek test was 68.5% sensitive and 99.5% specific. Darkfield detection for T. pallidum was 39% sensitive and 82% specific, in contrast to rapid plasma reagin and fluorescent treponemal antibody absorption test, which was 66% sensitive and 90% specific. Clinical diagnosis alone or in combination with basic laboratory tests showed poor agreement with M-PCR.

PIP: The etiology of genital ulcer disease (GUD) and the relationship between GUD and HIV infection were investigated in 302 patients presenting to a sexually transmitted disease clinic in Pune, India, in a 3-month period in 1994. Swabs of each genital ulcer were tested for herpes simplex virus (HSV) antigen by enzyme immunoassay and processed in a multiplex polymerase chain reaction (M-PCR) assay for simultaneous detection of HSV, Treponema pallidum, and Haemophilus ducreyi. The seroprevalence of HIV in this series was 22.2%. Clinical diagnosis of GUD was undermined when HIV infection was present. The etiology of GUD according to M-PCR was HSV in 26%, chancroid in 23%, primary syphilis in 10%, and multiple infections in 7%; no etiology could be identified in the remaining 34% of cases. Attempts to differentiate the etiology of GUD based solely on clinical grounds resulted in many inaccurate diagnoses. Chancroid was the most common clinical diagnosis (40%), followed by HSV (24%), syphilis (20%), and multiple infections (3%). HIV seroprevalence was significantly higher in patients with HSV compared with other etiologies (odds ratio, 2.1; 95% confidence interval, 1.2-3.7), presumably as a result of HIV-induced immunosuppression and consequent HSV reactivation. Until rapid, inexpensive, and sensitive assays become available, syndromic treatment with antibiotics should be provided to patients with GUD in order to reduce the risk of acquiring HIV infection.