Susan O. Ross

Association between Culturable Human Immunodeficiency Virus Type 1 (HIV-1) in Semen and HIV-1 RNA Levels in Semen and Blood: Evidence for Compartmentalization of HIV-1 between Semen and Blood

Both qualitative and quantitative virologic measurements were compared between blood and genital compartments for 128 men infected with human immunodeficiency virus type 1 (HIV-1) to address several controversial issues concerning HIV-1 shedding in semen and to obtain further information about the distribution of virus between these two compartments. Evidence for viral compartmentalization was suggested by earlier studies that noted the poor correlation between blood and seminal virus load, phenotype, and genotype. Further support for this viral compartmentalization was based on the following observations between semen and blood: lack of association between culturability of virus in semen and viral RNA level in blood, discordant distribution of viral phenotypes, discordant viral RNA levels, a weak correlation between viral RNA level in semen and CD4 cell count in blood, differences in the biologic variability of viral RNA levels, and differences in the virus load response to antiretroviral therapy.

Chronic prostatitis: epidemiology and role of infection.

We review the epidemiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and the role of infectious agents, emphasizing critical data necessary to define current research issues. The epidemiologic literature is limited, but the worldwide prevalence appears to be in the range of 2% to 10%, indicating that CP/CPPS represents an important international health problem. Recent molecular studies have documented bacterial DNA sequences in prostate tissue from CP/CPPS patients. These data suggest that colonization and/or infection occurs in the prostates of many patients with CP/CPPS. Further molecular research is needed to define the role of bacteria in the etiology of CP/CPPS.

BACTERIAL DNA SEQUENCES IN PROSTATE TISSUE FROM PATIENTS WITH PROSTATE CANCER AND CHRONIC PROSTATITIS

PURPOSE Although bacterial genetic material has been detected in prostate tissue from patients with various disorders, the prevalence of these organisms is unknown. We tested the hypothesis that bacterial detection rates differ between patients with prostate cancer and those with the chronic prostatitis/pelvic pain syndrome. MATERIALS AND METHODS Sterile prostate biopsies were obtained during radical retropubic prostatectomy from 107 patients with prostate cancer and using a perineal approach from 170 with the chronic prostatitis/pelvic pain syndrome. Numerous controls were also evaluated. Bacterial ribosomal encoding DNA (165 rDNA) sequences were detected using a polymerase chain reaction assay. Selected positives were cloned, sequenced and compared with DNA databases. RESULTS Bacterial DNA sequences were detected in 21 (19. 6%) of 107 patients with prostate cancer compared to 79 (46.4%) of 170 with chronic prostatitis (p <0.0001). These bacteria included urogenital pathogens, other described microorganisms and bacteria not reported previously. CONCLUSIONS Bacterial DNA sequences may be identified in prostate tissue from many patients. Bacterial detection rates in prostate tissue appear to differ among populations, with higher rates among patients with the chronic prostatitis/pelvic pain syndrome than among those with prostate cancer. Future studies of the role of various bacteria in the prostate may provide insight into the pathophysiology of prostate disease.

VASECTOMY AND HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 IN SEMEN

PURPOSE Human immunodeficiency virus type 1 (HIV) is cultured more often from seminal cells than seminal plasma. Because vasectomy causes dramatic reductions in seminal cells and also eliminates secretions from proximal sites in the male reproductive tract, vasectomy may change the potential infectiousness of semen. MATERIALS AND METHODS We used polymerase chain reaction (PCR) assays to measure HIV ribonucleic acid (RNA) in seminal plasma and HIV deoxyribonucleic acid (DNA) in seminal cells from 46 asymptomatic, seropositive men before and after vasectomy. RESULTS HIV RNA levels in semen correlated only weakly with blood levels (r = 0.22, p = 0.03). Of 183 semen specimens assayed for cell-free HIV RNA and proviral DNA 37 (20%) were positive for HIV RNA only, 41 (22%) were positive for HIV DNA only, and 18 (10%) were positive for RNA and DNA. Thus, detection of HIV RNA in seminal plasma was not associated with detection of HIV DNA in seminal cells. HIV RNA was present in 23 of 82 specimens (28%) (mean 2.87 log copies/ml.) before vasectomy and in 38 of 121 specimens (31%) after vasectomy (mean 2.81 log copies/ml.). CONCLUSIONS These findings suggest that direct measurement of HIV levels in semen is necessary to assess the potential for sexual transmission, most cell-free HIV in seminal plasma arises distal to the vas deferens, and vasectomy may have minimal impact on the infectiousness of HIV seropositive men on sexual partners.

Urinary tract infections in healthy university men

Acute symptomatic urinary tract infections occurred spontaneously in healthy university men. The mean incidence was 5 symptomatic infections per 10,000 men per year. Men with symptomatic infections were older than other students (p = 0.001) and 90% were sexually active. Of 38 patients 35 (92%) responded to a single course of antimicrobial therapy. Factors implicated in other male populations, such as anatomical abnormalities, urinary tract instrumentation, bacterial prostatitis and lack of circumcision, were seldom identified. Extensive evaluation appears unnecessary for young men with bacteriuria who respond to antimicrobial therapy.

DOES THE CHRONIC PROSTATITIS/PELVIC PAIN SYNDROME DIFFER FROM NONBACTERIAL PROSTATITIS AND PROSTATODYNIA?

PURPOSE The new consensus classification considers the chronic prostatitis/pelvic pain syndrome (CPPS) based on presence or absence of leukocytes in the expressed prostatic secretions, post-massage urine or seminal fluid analysis. We compared classification based on evaluation of these 3 specimens to the traditional classification based on expressed prostatic secretion examination alone. MATERIALS AND METHODS A prospective clinical and laboratory protocol was used to evaluate symptomatic patients who had no evidence of urethritis, acute bacterial prostatitis or chronic bacterial prostatitis. RESULTS Thorough clinical and microbiological evaluation of 310 patients attending our prostatitis clinic was used to select a population of 140 subjects who provided optimal expressed prostatic secretion, post-massage urine and semen specimens. Inflammation was documented in 111 (26%) of 420 samples, including 39 expressed prostatic secretion samples with 500 or greater leukocytes/mm.3, 32 post-massage urine samples with 1 or greater leukocytes/mm.3 and 40 seminal fluid specimens with 1 or greater million leukocytes/mm.3. Of the 140 subjects 73 (52%) had inflammatory chronic prostatitis/pelvic pain according to the consensus criteria but only 39 (28%) had nonbacterial prostatitis according to traditional expressed prostatic secretion criteria (p <0.001). CONCLUSIONS The new consensus concept of inflammatory chronic prostatitis/pelvic pain includes almost twice as many patients as the traditional category of nonbacterial prostatitis.

Male Genital Tract Compartmentalization of Human Immunodeficiency Virus Type 1 (HIV)

We present phylogenetic evidence supporting viral compartmentalization between the blood (peripheral blood mononuclear cells or plasma) and multiple genitourinary sites in HIV-infected men. Four of the five subjects evaluated demonstrated compartmentalization of viral sequences between urogenital tract specimens (tissue or fluid) and at least one blood category. HIV sequence migration from blood to urogenital tract was detected in four of five men, with migration from urogenital tract to blood in the fifth, and cross migration between both compartments noted in one man. These observations add 5 additional cases to the 27 total reported cases in which male urogenital tract compartmentalization has been studied, investigate surgical samples/specimens that have not been evaluated previously, and provide further evidence for restricted flow of HIV between the blood and the genital tract. As such, our study findings are important for understanding the long-term response to antiretroviral therapy, the design of vaccines, and the sexual transmission of HIV.

Lower genitourinary tract sources of seminal HIV

Objective: To investigate genital tract sources of HIV-1, we conducted extensive genitourinary sampling of 23 seropositive men without urethritis who shed HIV in their seminal plasma. Design: Semen was collected, then samples were obtained for HIV RNA in blood plasma, urethral fluid, pre-prostate massage fluid/urine (PMF/U) and post-PMF/U, and expressed prostatic secretions. Systematic transrectal ultrasound-guided prostate biopsies obtained from multiple prostate areas were evaluated for HIV RNA and DNA. Results: Seminal HIV RNA levels correlated with HIV RNA levels in urethral fluid and post-PMF/U and with prostate biopsies HIV DNA, but not with expressed prostatic secretions HIV RNA. However, only the HIV RNA level in post-PMF/U independently predicted that in semen (2.77-fold change in semen for each 10-fold change in post-PMF/U; 95% confidence interval, 1.0-7.7) accounting for one third of the seminal HIV RNA level variation, irrespective of adjustment for antiretroviral therapy. Conclusions: These data indicate that distal genitourinary sources other than the prostate appear to be the major source of seminal HIV in men without clinical urethritis or prostatitis. Because the HIV RNA level in blood plasma is not reliable as an independent clinical predictor of virus levels in seminal plasma, these findings also extend the concept that the male genital tract is a distinct virological compartment from blood.

Symptoms and inflammation in chronic prostatitis/chronic pelvic pain syndrome ☆

OBJECTIVES To evaluate the possibility that patients with inflammatory and noninflammatory chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) might present with different symptoms. Patients with CP/CPPS present with characteristic symptoms without bacteriuria. The new National Institutes of Health consensus suggests that CP/CPPS can be divided into inflammatory and noninflammatory categories. METHODS Standardized symptom surveys were completed by 130 subjects who met the criteria for CP/CPPS after clinical examination and urethral, urine, expressed prostatic secretion (EPS), and seminal fluid analysis evaluations. RESULTS When classified by either EPS or postprostatic massage urine (VB3) findings, subjects with and without inflammation had similar symptoms. However, when classified using the combination of EPS, VB3, and seminal fluid analysis, subjects with inflammatory CP/CPPS had more severe (P <0.02) and more frequent symptoms, in particular, difficulty reaching erection (P <0.01), weak urinary stream (P <0.01), urinary frequency (P = 0.03), and penile pain (P = 0.04). CONCLUSIONS The increased severity and frequency of symptoms among patients with inflammatory CP/CPPS provide empirical support for the new consensus classification on the basis of the combination of EPS, VB3, and seminal fluid analysis findings.

Counting leukocytes in expressed prostatic secretions from patients with chronic prostatitis/chronic pelvic pain syndrome

OBJECTIVES The evaluation of WBCs in EPS is recommended for classifying patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) but no agreement has been reached on the optimal method. We sought to determine the relationship between the expressed prostatic secretions (EPS) leukocyte (WBC) count per high-power field (evaluated by a more quantitative wet mount method and the traditional gram-stained smear method used in clinical microbiology laboratories) and the EPS WBC concentration to determine whether quantitative methods are necessary for accurate patient classification. METHODS EPS collected from 94 patients with CP/CPPS were evaluated by gram-stained smear, a standardized wet mount, and a hemocytometer method. RESULTS The gram-stained smear detected EPS WBCs in 21 (22%) of 94 subjects compared with 78 (83%) by the standardized wet mount and 57 (60%) by the hemocytometer method. The gram-stained EPS WBC count correlated poorly with the WBC concentration by hemocytometer (R(2) = 0.051, P = 0.03). Although the standardized EPS WBC count correlated better with the concentration by hemocytometer, the correlation coefficient remained low (R(2) = 0.244, P <0.0001). CONCLUSIONS The standardized wet mount proved superior to the gram-stained smear, but both methods lacked precision. Quantitative determination of the EPS WBC concentration by a counting chamber method proved to be the superior evaluation for research studies of CP/CPPS.