Defensins May Flag Silent PID.
Defensins are small antimicrobial peptides found in neutrophil granules and released in the early response to infection. They possess activity against both gram-positive and gram-negative bacteria. They are stable during prolonged storage, making them a good candidate for a diagnostic test for an inflammatory infectious process. Defensins have been shown to be elevated in patients with lower genital tract STDs, sepsis, and meningitis.
There is at present no entirely satisfactory diagnostic test for pelvic inflammatory disease (PID). Physical examination is of limited value, since its sensitivity is only about 65%. Laparoscopy--the diagnostic gold standard--is expensive and entails a small surgical risk. So the search is on for easily measurable markers of upper genital tract infection, according to Dr. Wiesenfeld of the University of Pittsburgh.
Asymptomatic PID as well as PID with atypical signs and symptoms are common conditions that have been linked by mounting evidence to fallopian tube damage as manifest by tubal factor infertility and ectopic pregnancy. Studies have shown that 23%-91% of women with tubal factor infertility have serologic evidence of prior chiamydial infection, and that more than 60% of woman with tubal factor infertility have evidence of prior gonococcal infection. The majority of these women deny any history of the classic PID symptoms, he noted.
Dr. Wiesenfeld reported on 314 women aged 15-30, deemed at high risk for unrecognized PID. They were mainly enrolled at a county STD clinic, where they were being seen for gonorrhea or chlamydial infections, bacterial vaginosis, mucopurulent cervicitis, or because they were sexual contacts of men with gonorrhea, chlamydial infection, or nongonococcal urethritis.
Endometrial biopsies were obtained in all participants to identify those with early PID as demonstrated by histologic endometritis, defined by at least five polymorphonuclear cells per high-power field and at least one plasma cell per low-power field.
Vaginal fluid defensin levels as measured by an enzyme-linked immunosorbent assay not commercially available proved to be elevated in women with early PID in this National Institutes of Health--sponsored study. The median vaginal fluid defensin level in the 12% of subjects with histologic endometritis was 2,647 ng/mL, compared with 1,049 ng/mL in the 64% of subjects with no endometritis and 481 ng/mL in those with plasma cell endometritis.
Using as a diagnostic cutoff point the median value of 1,108 ng/mL, vaginal fluid defensin measurement had a 78% diagnostic sensitivity and 54% specificity. The positive predictive value of the test was 18%, with a negative predictive value of 95%, Dr. Wiesenfeld said at the meeting, also sponsored by the American College of Obstetricians and Gynecologists.
Elevated vaginal fluid defensin levels were also noted in women with lower genital tract gonococcal or trichomonal infections, but not in those with chlamydia, bacterial vaginosis, yeast infections, or no STDs. However, after adjusting statistically for lower genital tract STDs and other variables in a multivariate logistic regression, elevated vaginal fluid defensins remained associated with a 3.5-fold increased risk of unrecognized PID.
There are, however, some kinks to be worked out before the test is ready for prime time, Dr. Wiesenfeld conceded. One is that increased frequency of sexual activity in this high-risk cohort was associated with lower--not higher--vaginal fluid defensin levels.
Nevertheless, scientific program chair Dr. James A. McGregor hailed Dr. Wiesenfeld's study as one of the most important presented at the meeting.
Dr. McGregor told this newspaper that a simple point-of-care test for PID would be of enormous clinical value and that he was unfazed by the defensin test's mere 18% positive predictive value in light of the seriousness of the condition the test aims to detect.