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Biomedical subjects

W E Stamm

Publications and source records attributed to W E Stamm.

At least 19 recordsLinked to original sources

Prevention of pelvic inflammatory disease by screening for cervical chlamydial infection.

BACKGROUND: Chlamydia trachomatis is a frequent cause of pelvic inflammatory disease. However, there is little information from clinical studies about whether screening women for cervical chlamydial infection can reduce the incidence of this serious illness. METHODS: We conducted a randomized, controlled trial to determine whether selective testing for cervical chlamydial infection prevented pelvic inflammatory disease. Women who were at high risk for disease were identified by means of a questionnaire mailed to all women enrollees in a health maintenance organization who were 18 to 34 years of age. Eligible respondents were randomly assigned to undergo testing for C. trachomatis or to receive usual care; both groups were followed for one year. Possible cases of pelvic inflammatory disease were identified through a variety of data bases and were confirmed by review of the women's medical records. We used an intention-to-screen analysis to compare the incidence of pelvic inflammatory disease in the two groups of women. RESULTS: Of the 2607 eligible women, 1009 were randomly assigned to screening and 1598 to usual care. A total of 645 women in the screening group (64 percent) for chlamydia; 7 percent tested positive and were treated. At the end of the follow-up period, there had been 9 verified cases of pelvic inflammatory disease among the women in the screening group and 33 cases among the women receiving usual care (relative risk, 0.44; 95 percent confidence interval, 0.20 to 0.90). We found similar results when we used logistic-regression analysis to control for potentially confounding variables. CONCLUSIONS: A strategy of identifying, testing, and treating women at increased risk for cervical chlamydial infection was associated with a reduced incidence of pelvic inflammatory disease.

Adolescent

Seroprevalence to Bartonella quintana among patients at a community clinic in downtown Seattle.

In 1993, an outbreak of 10 cases of Bartonella quintana bacteremia occurred among homeless, alcoholic, human immunodeficiency virus (HIV)-negative persons in Seattle. To estimate the prevalence of past exposure B. quintana among this population, a serosurvey was conducted in 1994 among patients at a downtown Seattle clinic. Microimmunofluorescent titers to B. quintana in 192 clinic patients were compared with titers in 199 age- and sex-matched Seattle volunteer blood donors. Titers > or = 64 were detected in 20% (39/192) of clinic patients compared with 2% (4/199) of blood donors (P<.001). Among clinic patients, alcohol abuse was independently associated in multivariate analysis with titers > or = 64 (odds ratio, 3.3; 95% confidence interval, 1.6-6.9). Of the 39 patients with B. quintana titers > or = 64, 24 (62%) also had titers > or = 64 to Bartonella henselae, indicating serologic cross-reactivity between Bartonella species. These results suggest that a substantial proportion of this indigent, inner-city Seattle population was infected with B. quintana.

Adolescent

Contraceptive methods and the risk of Chlamydia trachomatis infection in young women.

To evaluate the relation between contraceptive methods and cervical Chlamydia trachomatis infection, the authors studied a population-based sample of 1,779 nonpregnant women aged 15-34 years who underwent cell culture diagnostic testing for the detection of C. trachomatis at a health maintenance organization. Barrier contraceptive method users were classified as those who reported using one of the following methods at time of testing: condom, diaphragm, cervical cap, spermicidal sponge, foam, or vaginal spermicidal suppositories. Barrier methods were associated with a reduction in the risk of chlamydial infection in women aged 25 years or older when compared with all other women in the same age category (adjusted prevalence odds ratio = 0.15, 95% confidence interval (CI) 0.04-0.66). When compared with only noncontracepting women, the adjusted prevalence odds ratio was 0.34 (95% CI 0.06-1.99). The protective effect of barrier methods was not evident in women younger than age 25 years. Oral contraceptive use was not associated with the risk of C. trachomatis infection using either referent group; the adjusted prevalence odds ratio was 0.99 (95% CI 0.57-1.73) compared with all other women, and 0.88 (95% CI 0.44-1.79) compared with noncontracepting women. These findings suggest that present patterns of use of barrier methods differ by age and afford only selective protection against cervical C. trachomatis infections.

Adolescent

Azithromycin for empirical treatment of the nongonococcal urethritis syndrome in men. A randomized double-blind study.

OBJECTIVE: To evaluate the use of single-dose azithromycin for empirical treatment of nongonococcal urethritis. DESIGN: Randomized, double-blind, multicenter trial comparing azithromycin vs doxycycline therapy, with a 2:1 randomization ratio. Patients were evaluated clinically and microbiologically for Chlamydia trachomatis and Ureaplasma urealyticum infection before therapy and at 2 and 5 weeks after study entry. SETTING: Eleven sexually transmitted disease clinics throughout the United States. PATIENTS: A total of 452 men aged 18 years or older with symptomatic nongonococcal urethritis of less than 14 days' duration. INTERVENTION: Patients were treated with either 1.0 g of azithromycin as a single oral dose or 100 mg of doxycycline taken orally twice daily for 7 days. MAIN OUTCOME MEASURES: Clinical resolution of symptoms and signs of nongonococcal urethritis, microbiological cure of C trachomatis and U urealyticum, and occurrence of adverse experiences. RESULTS: Of the 452 patients enrolled, 248 in the azithromycin-treated group and 123 in the doxycycline-treated group were evaluable for clinical response. The two treatment groups were comparable in terms of age, weight, ethnic distribution, sexual preference, sexual activity, and history of prior nongonococcal urethritis or gonorrhea. Sixteen percent of the azithromycin group and 24% of the doxycycline group were culture positive for C trachomatis before therapy, while 38% and 28%, respectively, were culture positive for U urealyticum. The cumulative clinical cure rate was 81% (95% confidence interval [CI], 75% to 85%) in the azithromycin-treated group and 77% (95% CI, 69% to 84%) in the doxycycline-treated group. Clinical cure rates in the two groups were also comparable when patients were stratified by presence or absence of infection with C trachomatis or U urealyticum prior to therapy. Among those infected with C trachomatis, overall microbiological cure rates were 83% (95% CI, 65% to 94%) for azithromycin-treated patients (n = 30) and 90% (95% CI, 68% to 98%) for doxycycline-treated patients (n = 21). Among those infected with U urealyticum, overall microbiological cure rates were 45% (95% CI, 34% to 57%) for azithromycin-treated patients (n = 75) and 47% (95% CI, 30% to 65%) for doxycycline-treated patients (n = 32). Adverse reactions were generally mild to moderate and occurred in 23% of the azithromycin-treated group and 29% of the doxycycline-treated group. CONCLUSIONS: For empirical treatment of the acute nongonococcal urethritis syndrome in men, a single oral dose of azithromycin was as effective as a standard 7-day course of doxycycline in achieving clinical cure. Further, clinical cure rates were comparable with either regimen, regardless of the presence or absence of Chlamydia or Ureaplasma infection.

Adult

Diagnosis of Chlamydia trachomatis genitourinary infection in women by ligase chain reaction assay of urine.

Genitourinary infection with Chlamydia trachomatis is a common and potentially serious sexually transmitted disease. Diagnosis of C trachomatis infection in women typically relies on culture of endocervical swabs, an invasive and expensive procedure. The ligase chain reaction (LCR) is an in-vitro nucleic acid amplification technique that exponentially amplifies selected DNA sequences. We have compared an LCR-based assay to detect C trachomatis plasmid DNA in first void urine with culture of endocervical swabs for matched specimens from 1937 women from four geographic regions. Discordant specimen pairs were further tested by direct fluorescent antibody staining for elementary bodies and an alternative LCR assay based on the chlamydial outer membrane protein gene. An "expanded gold standard" was defined to include all culture-positive as well as culture-negative, confirmed LCR-positive women. The sensitivity and specificity of the LCR assay with first void urine samples compared with the expanded gold standard were 93.8% and 99.9%, respectively; the corresponding values for culture were 65.0% and 100%, respectively. Thus, an automated LCR assay of readily obtained urine samples showed a detection rate for infected women almost 30% greater than that of endocervical swab culture. The LCR assay was highly effective for the detection of C trachomatis in urine from women with or without signs or symptoms of chlamydial genitourinary tract infection.

Bacterial Outer Membrane Proteins

Randomized comparative trial and cost analysis of 3-day antimicrobial regimens for treatment of acute cystitis in women.

OBJECTIVE: To determine the efficacy, safety, and costs associated with four different 3-day regimens for the treatment of acute uncomplicated cystitis in women. DESIGN: A prospective randomized trial with a cost analysis. STUDY POPULATION: Women with acute cystitis attending a student health center. INTERVENTIONS: Treatment with 3-day oral regimens of trimethoprim-sulfamethoxazole, 160 mg/800 mg twice daily, macrocrystalline nitrofurantoin, 100 mg four times daily, cefadroxil, 500 mg twice daily, or amoxicillin, 500 mg three times daily. RESULTS: Six weeks after treatment, 32 (82%) of 39 women treated with trimethoprim-sulfamethoxazole were cured compared with 22 (61%) of 36 treated with nitrofurantoin (P = .04 vs trimethoprim-sulfamethoxazole), 21 (66%) of 32 treated with cefadroxil (P = .11 vs trimethoprim-sulfamethoxazole), and 28 (67%) of 42 treated with amoxicillin (P = .11 vs trimethoprim-sulfamethoxazole). Persistence of significant bacteriuria was less common with trimethoprim-sulfamethoxazole (3%) and cefadroxil (0%) compared with nitrofurantoin (16%; P = .05 vs trimethoprim-sulfamethoxazole) and amoxicillin (14%; P = .11 vs trimethoprim-sulfamethoxazole). Persistence of bacteriuria was associated with amoxicillin-resistant strains in the amoxicillin group but nitrofurantoin-susceptible strains in the nitrofurantoin group. Trimethoprim-sulfamethoxazole was more successful in eradicating Escherichia coli from rectal cultures soon after therapy and from urethral and vaginal cultures at all follow-up visits compared with the other treatment regimens. Adverse effects were reported by 16 (35%) of 46 patients receiving trimethoprim-sulfamethoxazole, 18 (43%) of 42 receiving nitrofurantoin, 12 (30%) of 40 receiving cefadroxil, and 13 (25%) of 52 receiving amoxicillin. The mean costs per patient were less with trimethoprim-sulfamethoxazole ($114) and amoxicillin ($131) compared with nitrofurantoin ($155) and cefadroxil ($155). CONCLUSIONS: A 3-day regimen of trimethoprim-sulfamethoxazole is more effective and less expensive than 3-day regimens of nitrofurantoin, cefadroxil, or amoxicillin for treatment of uncomplicated cystitis in women. The increased efficacy of trimethoprim-sulfamethoxazole is likely related to its antimicrobial effects against E coli in the rectum, urethra, and vagina.

Acute Disease

Infection with Chlamydia trachomatis lymphogranuloma venereum serovar L1 in homosexual men with proctitis: molecular analysis of an unusual case cluster.

Among 767 rectal isolates of Chlamydia trachomatis obtained from men over the period 1981-1991, 7 were found to be a rare lymphogranuloma venereum serovar, L1. These isolates were from rectal specimens taken from five male patients in 1982-1983. Six of the seven isolates were available for DNA sequencing studies. All six of these isolates shared the same DNA sequence in the major outer membrane protein (MOMP) gene variable domains and had different MOMP sequences than did the prototype L1, L2, and L3 strains, suggesting a point source outbreak. All five patients infected with serovar L-1 were homosexual men who had symptomatic proctitis characterized by rectal pain, discharge, tenesmus, abnormalities seen on anoscopy, and leukocytes seen on gram stains of rectal specimens. We conclude that an unrecognized point source outbreak of the rare chlamydial L1 serovar occurred among homosexual men in Seattle in 1982-1983, and that the clinical manifestations of L1 infection may be less severe than those of L2 infections.

Adult

Effect of secretor status on vaginal and rectal colonization with fimbriated Escherichia coli in women with and without recurrent urinary tract infection.

The prevalence and duration of rectal and vaginal colonization with P- and F-fimbriated Escherichia coli and the relationship of colonization with these strains to blood group secretor status was investigated. Rectal and vaginal E. coli isolates were prospectively collected twice monthly for 6 months from 20 young women with and 20 without a history of recurrent urinary tract infection (UTI). Rectal and vaginal colonization with P- and/or F-fimbriated E. coli was highly prevalent. Nonsecretors who developed UTI during the study period were significantly more likely to be colonized rectally with F-fimbriated E. coli than were the infected secretors (56% vs. 27%; P = .042) or uninfected nonsecretors (56% vs. 31%; P = .046). Persistent vaginal and rectal E. coli colonization with fimbriated organisms occurred commonly in the study patients but was not often temporally associated with the development of UTI. Results suggest that nonsecretors are more susceptible than secretors to colonization with F adhesin-bearing E. coli isolates.

Adhesins, Escherichia coli

Hemagglutination, adherence, and surface properties of vaginal Lactobacillus species.

To address the poorly understood mechanisms through which lactobacilli adhere to vaginal epithelial cells (VECs), 65 wild type lactobacilli isolated from the vaginal flora of young women and 3 American Type Culture Collection Lactobacillus strains were studied. Group I isolates (n = 56) hemagglutinated sheep, rabbit, and human red blood cells (RBCs) and adhered poorly to VECs. In contrast, all 4 group II strains hemagglutinated sheep and human but not rabbit RBCs, adhered in large numbers to VECs, and were identical in five phenotypic tests and DNA-DNA hybridization. Eight other strains (group III) hemagglutinated all RBC types studied, adhered avidly to VECs, and had identical protein and hybridization patterns but showed heterogeneous enzyme activities. Although most wild type lactobacilli from the vaginal flora of young women adhered poorly to VECs, selected isolates (groups II and III) adhered in large numbers, demonstrated specific and reproducible hemagglutination patterns, and may have specific mechanisms of attachment to VECs.

Animals

Chromosomal restriction fragment length polymorphism analysis of Escherichia coli strains causing recurrent urinary tract infections in young women.

To determine whether recurrent, symptomatic urinary tract infections (UTIs) in a given individual are due to the same or different strains, 71 Escherichia coli strains that caused recurrent UTIs were prospectively collected from 23 infection-prone young women and studied by chromosomal restriction fragment length polymorphism (RFLP) analysis using pulsed-field gel electrophoresis. Thirty-five strains from women with first-episode UTIs were also studied. Overall, 30 (68%) of 44 recurrent UTIs were caused by a strain previously identified in that person. In contrast, 32 of 35 strains from first-episode UTIs had unique RFLP profiles. Analysis of a subset of subjects established that the majority of recurrent UTIs were due to reinfection, not persistence of the pathogen within the urinary tract, and suggested that the colonic flora was the reservoir for these reinfecting strains.

Adolescent

Sequence conservation in the major outer membrane protein gene among Chlamydia trachomatis strains isolated from the upper and lower urogenital tract.

To determine the extent of nucleotide sequence variation in the major outer membrane protein (MOMP) gene among 27 clinical isolates of Chlamydia trachomatis, the MOMP gene was amplified from 13 strains isolated from the endometrium of patients with pelvic inflammatory disease and high titers of anti-chlamydial antibodies and from 14 strains isolated from the cervix of patients with presumed first-time chlamydial infection. Amplified MOMP variable domain DNA from these isolates was directly sequenced and compared with previously published results. Very little sequence heterogeneity in the MOMP variable domains was found in all 27 clinical isolates, suggesting that MOMP sequence heterogeneity is not often associated with the spread of C. trachomatis to the upper genital tract and is not common in the chlamydial strains in the patient population studied.

Amino Acid Sequence

Characterization of the hemolytic activity of Haemophilus ducreyi.

H. ducreyi is the causative agent of chancroid, a genital ulcer disease most prevalent in developing countries. Chancroid enhances the heterosexual transmission of human immunodeficiency virus and is identified in focal outbreaks in the United States, but little is known about its pathogenesis. We studied the hemolysin produced by H. ducreyi because this molecule might be an important virulence factor in the pathogenesis of chancroid. Ten strains of H. ducreyi were tested on newly devised blood agar plates and were found to have hemolytic activity. We examined the hemolytic activity of H. ducreyi 35000 further and found that it was heat labile, cell associated, greatest at pH 7.0, and produced in logarithmic- but not stationary-phase cultures. Using transposons Tn916 and Tn1545-delta 3, we have isolated three classes of transposon mutants of strain 35000: those with no detectable hemolytic activity, those with reduced hemolytic activity, and those with enhanced hemolytic activity. Transposon insertions in the nonhemolytic mutants were located in a DNA sequence which hybridized to the Proteus mirabilis hemolysin gene. Analysis of clones containing overlapping sections of this region served to further localize the H. ducreyi hemolysin gene and allow its expression in Escherichia coli and complementation of the nonhemolytic defect in an H. ducreyi mutant. These experiments indicate that H. ducreyi 35000 produces a hemolysin that is related to the calcium-independent hemolysin produced by P. mirabilis. Further experiments are needed to define the similarity of the H. ducreyi hemolysin to other calcium-independent hemolysins and to determine its role in the pathogenesis of chancroid.

Cloning, Molecular

Direct antimicrobial susceptibility testing for acute urinary tract infections in women.

Despite its theoretical advantages, direct antimicrobial susceptibility testing (DST) of urine specimens remains controversial largely because of concerns regarding its accuracy, particularly with mixed cultures. To evaluate the performance of DST in the setting of acute urinary tract infection (UTI), we performed DST using 25 traditional and contemporary antimicrobial agents on urine specimens from 162 women with suspected acute uncomplicated UTI, and compared these results with the results of standardized disk diffusion susceptibility tests done on the same specimens. Direct tests were interpretable for 129 specimens, i.e., 80% of all specimens and 85% of the 152 specimens that met the culture criteria for UTI. Of the 2,983 individual comparisons between the direct and standard tests, 0.8% represented very major errors, 0.6% represented major errors, 3.1% represented minor errors, and 95.5% were in agreement. Errors were more common in association with older antimicrobial agents and agents with a high prevalence of antimicrobial resistance, non-Escherichia coli strains, low urine bacterial concentrations, sparse or mixed growth in the direct test, and the presence of multiple significant organisms in urine. The urine leukocyte concentration was > or = 15/mm3 in all subjects and did not differentiate between specimens that gave an interpretable direct test and those that did not. Calculation of the sensitivity of DST in identifying antimicrobial resistance supplemented conventional error rate analysis. We conclude that when used selectively and interpreted carefully, DST of urine specimens offers an efficient, rapid, and accurate method for antimicrobial susceptibility determination for acute UTI, particularly when the urine bacterial concentration is > 10(5) CFU/ml.

Acute Disease

Risk of perinatal transmission of Chlamydia trachomatis by mode of delivery.

We compared the transmission rate of Chlamydia trachomatis infection from infected women to their infants after various modes of delivery. After vaginal birth, Chlamydia trachomatis was isolated from 58 of 125 infants with a cephalic presentation, and serological evidence of chlamydial infection was found in another eight. C. trachomatis was isolated from the only infant with a frank breech presentation. After Caesarean birth, C. trachomatis was isolated from two of 10 infants born after rupture of the membranes and from one of six without prior rupture of the membranes. No serological evidence of infection was found in any of the culture-negative infants born by Caesarean section. By survival analysis, rates of transmission were significantly lower after Caesarean section with rupture of the membranes before delivery than after vaginal delivery. Infants born to infected women are at risk of C. trachomatis infection regardless of route of delivery.

Cesarean Section

Effects of recent sexual activity and use of a diaphragm on the vaginal microflora.

We prospectively studied 40 women over a median period of 28 weeks to ascertain the effects on vaginal microflora of sexual intercourse alone compared with sexual intercourse associated with use of a diaphragm with a spermicide (diaphragm/spermicide). Compared with no sexual intercourse, sexual intercourse with use of a diaphragm/spermicide in the preceding 3 days was strongly associated with increases in rates of vaginal colonization with uropathogenic flora, including Escherichia coli (P < .0001), other gram-negative uropathogens (P = .0045), group D streptococci (P = .014), and group B streptococci (P = .0015). Except for E. coli colonization, no such increases in rates of vaginal colonization were seen at visits preceded by sexual intercourse without use of a diaphragm/spermicide. Compared with no sexual intercourse, sexual intercourse with use of a diaphragm/spermicide in the preceding 3 days also was associated with a marked increase in rates of candidal colonization (P < .0001) and with a decrease in rates of lactobacillus colonization (P < .0001). We conclude that bacterial and fungal microflora in the vagina are strongly influenced by recent use of a diaphragm/spermicide and minimally affected by sexual intercourse alone.

Adult

Clinical manifestations of genital infection due to Chlamydia trachomatis in women: differences related to serovar.

The relationship between the infecting Chlamydia trachomatis serovar and the clinical manifestations of genital tract infection was evaluated in a study of 155 women attending a sexually transmitted diseases clinic; 99 women had lower genital tract infection and 56 had Chlamydia-associated pelvic inflammatory disease (PID). In the group with lower genital tract infection, women with serovar F differed from those with serovars of class B or C in that they exhibited fewer signs of cervical infection, including easily induced bleeding (P = .04), edema of the zone of cervical ectopy (P = .06), and colposcopic evidence of mucopurulent endocervical discharge (P = .007). Serovar F also produced fewer infections with inclusion counts of > or = 1,000 and fewer rectal infections (P = .04). There was no apparent association of any specific serovar with PID. Thus, in this population, serovar F was associated with fewer objective clinical manifestations of mucopurulent endocervical discharge, and the distribution of chlamydial serovars found in PID reflected that found in lower genital tract infection.

Adult

O, K, and H antigens predict virulence factors, carboxylesterase B pattern, antimicrobial resistance, and host compromise among Escherichia coli strains causing urosepsis.

The O:K:H serotypes of 75 Escherichia coli blood isolates from patients with urosepsis were compared for the presence and expression of determinants for P fimbriae, hemolysin, and aerobactin; antimicrobial resistance; the carboxylesterase B phenotype; and associated compromising host conditions. O groups, K types, and O:K:H serotypes previously associated with urovirulence accounted for 69%, 60%, and 31% of the population, respectively. Chromosomal determinants for P fimbriae, hemolysin, and aerobactin were present in combination more commonly among strains belonging to urovirulence-associated O groups, K types, and O:K:H serotypes. Similarly, antimicrobial resistance was strikingly less prevalent, the B2 carboxylesterase phenotype more common, and associated host compromise less common among such strains. These data demonstrate that the O groups, K types, and O:K:H serotypes traditionally associated with urovirulence are prominent among E. coli strains causing urosepsis, in which they are associated with presence and expression of multiple chromosomal virulence factor determinants, susceptibility to antimicrobial agents, the B2 carboxylesterase phenotype, and noncompromised hosts.

Antigens, Bacterial

A primate model for chancroid.

Adult pigtailed macaques (Macaca nemestrina) were evaluated for their usefulness as a primate model for chancroid. To initiate infection, 10(7)-10(8) cfu of Haemophilus ducreyi were inoculated into the foreskins of 5 adult males and into the vaginal labia of 4 adult females. Lesions developed in the male macaques that were similar in appearance, histopathologic changes, and progression to those of human disease, including the development of ulcers 6-12 days after infection. In addition, H. ducreyi could be recovered from the lesions up to 20 days after inoculation, humoral antibodies were induced beginning 1 week after inoculation, and inguinal lymphadenopathy was noted in 4 of the 5 males. None of the 4 female macaques inoculated with the same preparation of live H. ducreyi developed comparable lesions. Thus, experimental chancroid in adult male macaques closely resembles human disease and should be useful for future studies of the pathogenesis of chancroid.

Animals