Male circumcision and HIV/AIDS Risk - Analysis of the scientific evidence

"Objective: The aim of this review was to evaluate the scientific evidence supporting the hypothesis that male circumcision reduces the risk of HIV infection and consequently the incidence of acquired immunodeficiency syndrome (AIDS). Patients and Methods: We performed a literature search of the major databases (Medline; Embase; Cochrane Library; Biosis and Science Citation Index) for papers published in the period 1999 to 2008; using the terms ""male circumcision""; ""HIV infection"" and ""sexually transmitted infection;"" plus the combination of the search terms ""foreskin"" and ""HIV receptor"" to identify 1;048 articles. We reviewed the abstracts to identify 278 articles meriting detailed review. This detailed review considered how well individual studies were designed and carried out; using a standard checklist to provide a systematic quality rating for individual studies. This process identified a total of 80 papers; which were rated following the level of evidence and grade of recommendation scales modified from the Oxford Center for Evidence-Based Medicine. Results: Detailed analysis of the selected articles on male circumcision and HIV infection risk revealed the following. Systematic reviews; meta-analyses and modeling studies: there were 11 papers; 10 positive (favoring circumcision) and 1 negative; of the 10 positive studies; 4 were level 3 evidence; 5 were level 2 and 1 was level 1 evidence. Randomized controlled trials: there were 3 studies; all positive with level 1 evidence. Non-randomized cohort studies: there were 6 papers; 5 were positive (2 level 3 and 3 level 2 evidence) and 1 was negative (level 3 evidence). Casecontrol studies: there were 12 studies; 11 positive (all level 3) and 1 negative (level 3 evidence). Case series: there were 2 studies; both positive (level 3 evidence). Expert opinion: there were 34 studies; 30 positive (15 level 4; 15 level 3 evidence); 2 negative (both level 4) and 2 neutral (both level 4 evidence). Cost-effectiveness studies: there were 3 studies; all positive; all level 2 evidence. Pertinent biological studies: there were 3 studies; all positive; all level 4 evidence. The three large; exceptionally well-done randomized; controlled trials of adult male circumcision among consenting; healthy men in three African countries enrolled a total of 10;908 uncircumcised; HIV-negative adult men. The cumulative HIV infection risk estimated using intention-to-treat Kaplan-Meier analysis showed an overall rate ratio (RR) of 0.42 (95confidence interval (CI) 0.31-0.57); corresponding to a protective effect of 58(95CI 43-69). Meta-analysis of the ""as-treated"" results of the three trials showed even stronger protection against HIV infection in the circumcision group (summary RR 0.35; 95CI 0.24-0.54). Conclusions: Rigorous analysis of the available scientific evidence clearly supports a positive recommendation that male circumcision should be actively promoted in populations at high risk of HIV infection. There is a need to provide safe male circumcision services for high-risk populations; because this is one of very few proven HIV prevention strategies. Male circumcision provides a much-needed addition to the limited HIV prevention armamentarium. The challenges to implementation must now be faced"

Classification, epidemiology and implications of chronic prostatitis in North America, Europe and Asia.

The last decade has seen a resurgence of interest and exciting new research on chronic prostatitis and related syndromes. One important reason for this enthusiasm is the recognition that chronic prostatitis syndromes represent an important worldwide health care problem. New data suggesting that chronic prostatitis syndromes may have important long-term consequences are a second reason for the resurgence of research interest. This article reviews the new classification of chronic prostatitis syndromes. Emphasis is then given to summarizing new data on the epidemiology of chronic prostatitis. We concentrated on population-based studies employing reasonable case-definitions to survey various populations from North America, Europe and Asia. These studies suggest that prostatitis syndromes are common, with 2-10% of adult men suffering from symptoms compatible with chronic prostatitis at any time. Approximately 15% of men suffer from symptoms of prostatitis at some point in their lives. Preliminary epidemiological and biological studies also suggest that chronic prostatitis may be associated with an increased risk for development of benign prostatic hyperplasia and prostate cancer. These findings support the conclusions that chronic prostatitis is an important international health care problem that merits increased priority from clinicians as well as increased clinical and basic science research.

Seminal fluid analysis in chronic prostatitis/chronic pelvic pain syndrome.

Prostatitis is a common cause of morbidity among adult men. There are more than 2,000,000 doctor visits per year in the United States, approximately half to urologists (Collins et al., 1998, J Urol 159:1224; Roberts et al., 1998, Urology 51:578; Krieger et al., 2003, Urology). The problem is that very few patients have obvious infections, or functional or structural abnormalities. The aim of this study is to examine our experience with seminal fluid analysis in this patient population, and to outline the potential utility of this examination in patient evaluation.

Short tandem repeat polymorphism linkage to the androgen receptor gene in prostate carcinoma.

BACKGROUND: Due to high polymorphism, common sequences, and ubiquitous presence, short tandem repeats (STRs) may enhance genomic typing to determine prostate carcinoma (CaP) predisposition. The human phosphoglycerate kinase (PGK1) gene is located within Xq11-Xq13, a region implicated in familial prostate carcinoma, androgen insensitivity, perineal hypospadias, and other genitourinary abnormalities. The PGK1 STR is the most polymorphic site described in the Xq11-Xq13 interval and was investigated for its ability to detect differences comparing a heterogeneous CaP population versus controls. METHODS: We compared PGK1 STR allele sizes in 103 localized CaP patients with 299 control subjects to evaluate the STR's ability to detect potential CaP predisposing genetic factors. Allele sizes were measured with an automated DNA sequencer after polymerase chain reaction (PCR) based copying of the PGK1 STR region. Allele sizes were compared using chi square and Mann-Whitney U tests. RESULTS: Among 402 subjects, there were 10 distinct allele sizes consisting of five common and five relatively rare alleles. The PGK1 STR, 12 allele (12 tetrameric repeats) was more common among patients with CaP (p=0.03). Allele 13 was more common in CaP patients > 60 years old than among younger patients (p< 0.005). CONCLUSIONS: Our findings suggest that STRs in the Xq11-Xq13 region and other regions may provide a means to rapidly scan genetic loci in large populations of CaP patients and controls. Within limitations, STRs offer the advantage of relatively uniform protocols that could potentially provide a means to comprehensively scan genomes at known predisposing loci.

Comparison of microscopic methods for detecting inflammation in expressed prostatic secretions.

PURPOSE: We evaluated microscopic methods of detecting inflammation in expressed prostatic secretions. MATERIALS AND METHODS: Methods of counting expressed prostatic secretion leukocytes were compared in 251 samples from 159 patients with chronic prostatitis/chronic pelvic pain syndrome, including traditional wet mounts, hemocytometer derived concentrations and expressed prostatic secretion smears stained with Gram's method or DiffQuick stain (Dade International, Inc., Miami, Florida). RESULTS: Of 159 initial patient evaluations 84 (53%) showed inflammation by hemocytometer concentration at 500 leukocytes per mm.3 or greater but only 37 (23%) were considered inflammation by the traditional wet mount method (p <0.001). Inflammation was identified in 149 of 251 specimens (59%) by hemocytometer but in only 82 (33%) by wet mount (p <0.001). When inflammation was defined as 1,000 leukocytes per mm.3 or greater the hemocytometer still identified significantly more patients (41%) and specimens (48%) with inflammation than the wet mount. The hemocytometer method had a substantially lower interassay and intra-assay coefficient of variation than the wet mount method. Polymorphonuclear neutrophils and macrophages were the most common cells observed on stained smears, which detected inflammation in 147 specimens (59%) by DiffQuick but in only 98 (39%) by Gram's method. CONCLUSIONS: Detecting inflammation in expressed prostatic secretions is method dependent. Significantly more cases of inflammation were detected by hemocytometer than by the traditional wet mount technique. Because the wet mount method also proved more variable than the hemocytometer and highly sensitive to volume, its use is not recommended. These findings support the adoption of hemocytometer and staining methods for accurate evaluation of expressed prostatic secretion inflammation in men with chronic prostatitis/chronic pelvic pain syndrome.

Consensus development of a histopathological classification system for chronic prostatic inflammation.

OBJECTIVE: To develop a standardized histopathological classification system for chronic prostatitis (standardized description of prostatic inflammatory infiltrates) based on a literature review, extensive prospective evaluations in two recognized prostatitis research centres and widespread consensus of international urological centres identified as having major expertise or interest in chronic prostatitis. METHODS: Relevant articles for review were identified by a Medline search undertaken by the Cochrane Review Group in Prostate Diseases and Urologic Malignancies, and cross-checking bibliographies of retrieved studies, reviews, book chapters and abstracts of the American Urological Association and International Prostatitis Collaborative Network Annual Meetings. Initial drafts were based on classification systems independently developed by the Prostatitis Research Centers at Queen's University in Canada and University of Washington in the USA. A collaborative draft was distributed to 20 urological/pathological clinical centres who participated in the North American Chronic Prostatitis Collaborative Research Network and First International Prostatitis Collaborative Network. A consensus classification system was then distributed to the participating panel for acceptance. RESULTS: The literature review identified a reasonably consistent description of inflammatory infiltrate locations and patterns that were further incorporated into the draft based on the Queen's University and University of Washington proposals. Eighteen (90%) of the identified Prostatitis Centers participated in the revision of the draft and the final consensus process. The final consensus document classifies prostatic inflammation according to its extent and grade/severity in each tissue compartment (location). Conclusion The consensus of the expert panel was that this classification system can be used in the evaluation of prostatic inflammation in prostate biopsies, transurethral resected prostate chips or prostatectomy specimens. A standardized accepted framework to describe histopathological prostate inflammation will prove useful in evaluating prostate disease.

Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: a probabilistic empiric model.

OBJECTIVE: To develop a model to predict transmission of HIV-1 from men to women. DESIGN: HIV-1 in seminal plasma, and endocervical CCR5 receptors were correlated with epidemiological studies of HIV-1 transmission to develop a probabilistic model. SETTINGS: Semen samples were collected from patient subjects in Seattle Washington, Chapel Hill, North Carolina, and St. Gallen, Switzerland. Endocervical biopsy specimens were obtained from women in Chicago, Illinois. PARTICIPANTS: Eighty-six men (not receiving antiretroviral therapy) in whom CD4 cell count and semen volume were available, and 24 women in whom the number of endocervical CCR5 receptors were determined. MAIN OUTCOME MEASURES: Prediction of transmission of HIV-1 from men to women per episode of vaginal intercourse based on the absolute burden of HIV (volume x HIV RNA copies/ml seminal plasma). RESULTS: The model suggests efficient heterosexual transmission of HIV-1 when semen viral burden is high. When semen contains 100 000 copies of non-syncytium-inducing (NSI) HIV RNA the probability of HIV-1 transmission is 1 per 100 episodes of intercourse; conversely, with 1000 copies NSI HIV RNA in semen, transmission probability is 3 per 10 000 episodes of intercourse. CONCLUSIONS: This model links biological and epidemiological data related to heterosexual HIV-1 transmission. The model can be used to estimate transmission of HIV from men with high semen viral burden from inflammation, or reduced burden after antiretroviral therapy. The results offer a biological explanation for the magnitude of the HIV epidemic in places where earlier studies have shown men have high semen viral burden, such as in sub-Saharan Africa. The model can be used to develop and test HIV-1 prevention strategies.

Comparison of complications after radical and partial nephrectomy: results from the National Veterans Administration Surgical Quality Improvement Program.

OBJECTIVE: To determine whether radical nephrectomy causes less morbidity, less mortality and is associated with a shorter hospital stay than is partial nephrectomy. PATIENTS AND METHODS: A total of 1885 nephrectomies (1373 radical and 512 partial) conducted between 1991 and 1998 in the Department of Veterans Affairs (VA) National Surgical Quality Improvement Program were evaluated. Using multivariate analyses, outcomes were risk-adjusted based on 45 preoperative variables to compare mortality and morbidity rates. RESULTS: The unadjusted 30-day mortality was 2.0% for radical and 1.6% for partial nephrectomy (P = 0.58). Risk-adjusting the two groups did not result in a statistically significant difference in mortality. The 30-day overall morbidity rate was 15% for radical and 16.2% for partial nephrectomy (P = 0.52); risk-adjusted morbidity rates were not statistically different. There were no statistically significant differences in the rates of postoperative progressive renal failure, acute renal failure, urinary tract infection, prolonged ileus, transfusion requirement, deep wound infection, or extended length of stay. CONCLUSIONS: Partial nephrectomy carried out in the VA program has low morbidity and mortality rates, comparable with the complication rates after radical nephrectomy.

Comparison of assays to detect cytomegalovirus shedding in the semen of HIV-infected men.

We sought to determine the optimal assays for cytomegalovirus (CMV) shedding in semen. Over a 2-month period, 149 HIV-1-infected men who have sex with men each provided up to three semen specimens. Specimens were tested for CMV by culture, rapid assay (shell vial) and polymerase chain reaction (PCR). By culture, 30% of seminal plasma and 28% of seminal cell specimens grew CMV. By rapid assay, results were 38 and 33%, respectively. By PCR, 56% of seminal cell specimens demonstrated CMV: 20% in a single semen specimen; 33% in two specimens; and 34% in all three specimens. Overall, 69% of men had CMV detected by PCR in at least one seminal cell specimen. By quantitative PCR, 14% had ten, 14% had 100, 16% had 1000, and 12% had 10000 copies in 6.25 microl of semen analyzed. Adjusting for initial CD4+ cell count, men with CMV shedding demonstrated by PCR at the first visit were approximately four times as likely to shed CMV at a subsequent visit (RR 4.28, CI: 2.30-7.95). CMV shedding was associated with decreased CD4+ cell counts in peripheral blood (P=0.05). It is concluded that the PCR assay provided the greatest sensitivity among the three detection methods.

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.

Prostate vascular flow: the effect of ejaculation as revealed on transrectal power Doppler sonography.

OBJECTIVE: The objective of our study was to determine the effect of ejaculation on prostate vascular flow. SUBJECTS AND METHODS: Using power Doppler technology, we performed four transrectal sonographic examinations before and immediately, 6 hr, and 24 hr after ejaculation in 10 healthy volunteers. Images were assessed by three independent observers. RESULTS: Ninety-seven percent of the images ranked as having the least flow were from the baseline examination. There was a significant difference between the rankings when categorized into the four time sets (mean score for the baseline group was 1.1, whereas for the immediate, 6-, and 24-hr postejaculation groups it was 2.5, 2.9, and 2.4, respectively (p<0.0001). The only statistically significant difference was between the baseline and the three remaining groups. Interobserver agreement was high, with the chance-corrected measure of agreement of 0.78. CONCLUSION: Transrectal sonography revealed that prostate vascular flow increases dramatically after ejaculation and remains elevated for at least 24 hr. This observation should be considered when power Doppler sonography is used to assess for potential hyperemia in patients suspected of having prostate abnormalities.

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.

Amniotic fluid interleukin-6 and preterm delivery: a review.

OBJECTIVE: To evaluate the potential role of amniotic fluid (AF) interleukin (IL)-6 as a predictor of preterm delivery and to consider possible explanations for the proportion of women with elevated AF IL-6 who deliver preterm yet lack microbiologically detectable intra-amniotic infection. DATA SOURCES: We searched the English language human literature in MEDLINE, 1966 through September 1999, using the keywords "labor/infant," "premature," "cytokines/interleukin-6," and "AF." We also examined abstracts from the 1999 meetings of the Society for Maternal-Fetal Medicine and the Society for Epidemiologic Research. We identified other studies by reviewing the reference lists of published articles. METHODS OF STUDY SELECTION: The MEDLINE search yielded 55 citations. We focused on studies that reported on the association between AF IL-6 and preterm delivery. TABULATION, INTEGRATION, AND RESULTS: There is consensus in the literature that elevated AF IL-6 is a stronger predictor of preterm delivery than intra-amniotic infection detected by either microbiologic culture or polymerase chain reaction (PCR). Among women with elevated AF IL-6, PCR could detect a higher proportion of intra-amniotic infection than culture. A number of women with elevated AF IL-6 (33-70%) deliver preterm and do not have evidence of intra-amniotic infection by either culture or PCR. Possible explanations for this observation are considered. CONCLUSION: Elevated AF IL-6 is strongly associated with preterm delivery and merits future consideration in clinical settings to predict preterm delivery and guide patient care. Development of improved polymerase chain reaction-based clinical methods to detect intra-amniotic infection is necessary to better understand the relationship between elevated AF IL-6, intra-amniotic infection, and preterm delivery.

Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons.

BACKGROUND: Most persons who have serologic evidence of infection with herpes simplex virus (HSV) type 2 (HSV-2) are asymptomatic. Historically, it has been assumed that these persons have less frequent viral reactivation than those with symptomatic infection. METHODS: We conducted a prospective study to investigate genital shedding of HSV among 53 subjects who had antibodies to HSV-2 but who reported having no history of genital herpes, and we compared their patterns of viral shedding with those in a similar cohort of 90 subjects with symptomatic HSV-2 infection. Genital secretions of the subjects in both groups were sampled daily and cultured for HSV for a median of 94 days. RESULTS: HSV was isolated from the genital mucosa in 38 of the 53 HSV-2-seropositive subjects (72 percent) who reported no history of genital herpes, and HSV DNA was detected by the polymerase-chain-reaction assay in cultures prepared from genital mucosal swabs in 6 additional subjects. The rate of subclinical shedding of HSV in the subjects with no reported history of genital herpes was similar to that in the subjects with such a history (3.0 percent vs. 2.7 percent). Of the 53 subjects who had no reported history of genital herpes, 33 (62 percent) subsequently reported having typical herpetic lesions; the duration of their recurrences in these subjects was shorter (median, three days vs. five days; P<0.001) and the frequency lower (median, 3.0 per year vs. 8.2 per year; P<0.001) than in the 90 subjects with previously diagnosed symptomatic infection. Only 1 of these 53 subjects had no clinical or virologic evidence of HSV infection. CONCLUSIONS: Seropositivity for HSV-2 is associated with viral shedding in the genital tract, even in subjects with no reported history of genital herpes.

Gentamicin for the practicing urologist: review of efficacy, single daily dosing and "switch" therapy.

PURPOSE: We review the literature on gentamicin, including single daily dosing and "switch" therapy. MATERIALS AND METHODS: We used MEDLINE to search the literature from 1966 to June 1997, and then manually searched bibliographies to identify studies that our initial search might have missed. RESULTS: Gentamicin has attractive characteristics, including wide spectrum, infrequent resistance, economy and familiarity. Although limited by well known toxicities, gentamicin remains a drug of choice for serious Gram-negative infections. Dosing strategies, such as single daily dosing and switch therapy, have renewed enthusiasm for this time-honored drug. CONCLUSIONS: Gentamicin remains a valuable drug in urology. Once daily dosing and switch therapy offer the potential to increase effectiveness and convenience while decreasing toxicity and costs.

Prostate blood flow characteristics in the chronic prostatitis/pelvic pain syndrome.

PURPOSE: We determine whether the chronic prostatitis/pelvic pain syndrome is associated with abnormal prostate blood flow. MATERIALS AND METHODS: We used color Doppler ultrasonography to examine 53 patients with inflammation, 80 men without inflammation and 22 healthy controls. Images were recorded and scored using standardized criteria to characterize the degree and distribution of prostatic vascularity. RESULTS: Flow was observed to the entire prostatic capsule in 77% of patients but only 18% of controls (p<0.0001). Parenchymal flow was evaluated using several criteria. On a 2-point scale flow was classified as grade 2 in 74% of patients compared to 27% of controls (p<0.0001). Similar findings were noted on a Doppler spot scale, with flow classified as grade 2 in 47% of patients compared to 14% of controls (p<0.004). Patients also had more parenchymal Doppler spots than controls (p<0.01). Diffuse blood flow throughout the prostatic parenchyma was observed in 63% of patients compared to 36% of controls (p<0.03). There was no significant difference in the amount or distribution of blood flow in patients with and without inflammation. CONCLUSIONS: The chronic prostatitis/pelvic pain syndrome was associated with increased blood flow to the prostatic capsule and diffuse flow throughout the prostatic parenchyma. Despite technical limitations, color Doppler ultrasonography may provide objective documentation of prostate blood flow abnormalities in patients with this syndrome.

Detecting urethral and prostatic inflammation in patients with chronic prostatitis.

OBJECTIVES: Diagnosis of urethral and prostatic inflammation can represent a challenge. We compare the accuracy of diagnostic methods for detecting inflammation in lower urinary specimens/samples. METHODS: A standardized protocol was used to evaluate urethral smear, first-void urine (VB1), midstream urine (VB2), expressed prostatic secretions (EPS), and postmassage urine (VB3) in urologic patients with no symptoms or signs of urethritis who were attending our prostatitis clinic. RESULTS: Of 235 subjects, 60 (26%) had leukocytes detected by the Gram-stained urethral smear, 44 (18%) by the VB1, and only 14 (6%) by the VB2. Compared with the urethral swab, VB1 had 0% to 22% sensitivity and 81% to 98% specificity, and VB2 had 8% to 11% sensitivity. Of 83 subjects with prostatic inflammation, the EPS detected 63 (76%) and the VB3 detected 68 (82%). CONCLUSIONS: VB1 or VB2 examinations had low sensitivity for detecting urethral inflammation. Examining both the EPS and VB3 proved best for detecting prostatic fluid inflammation. Combining the urethral smear with lower urinary tract localization ("four-glass test") represents an optimal approach for detecting urethral and prostatic inflammation.