David Sokal

Male circumcision for HIV prevention: current evidence and implementation in sub-Saharan Africa

Heterosexual exposure accounts for most HIV transmission in sub-Saharan Africa, and this mode, as a proportion of new infections, is escalating globally. The scientific evidence accumulated over more than 20 years shows that among the strategies advocated during this period for HIV prevention, male circumcision is one of, if not, the most efficacious epidemiologically, as well as cost-wise. Despite this, and recommendation of the procedure by global policy makers, national implementation has been slow. Additionally, some are not convinced of the protective effect of male circumcision and there are also reports, unsupported by evidence, that non-sex-related drivers play a major role in HIV transmission in sub-Saharan Africa. Here, we provide a critical evaluation of the state of the current evidence for male circumcision in reducing HIV infection in light of established transmission drivers, provide an update on programmes now in place in this region, and explain why policies based on established scientific evidence should be prioritized. We conclude that the evidence supports the need to accelerate the implementation of medical male circumcision programmes for HIV prevention in generalized heterosexual epidemics, as well as in countering the growing heterosexual transmission in countries where HIV prevalence is presently low.

Vasectomy by ligation and excision, with or without fascial interposition: a randomized controlled trial [ISRCTN77781689]

BackgroundRandomized controlled trials comparing different vasectomy occlusion techniques are lacking. Thus, this multicenter randomized trial was conducted to compare the probability of the success of ligation and excision vasectomy with, versus without, fascial interposition (i.e. placing a layer of the vas sheath between two cut ends of the vas).MethodsThe trial was conducted between December 1999 and June 2002 with a single planned interim analysis. Men requesting vasectomies at eight outpatient clinics in seven countries in North America, Latin America, and Asia were included in the study. The men were randomized to receive vasectomy with versus without fascial interposition. All surgeons performed the vasectomies using the no-scalpel approach to the vas. Participants had a semen analysis two weeks after vasectomy and then every four weeks up to 34 weeks. The primary outcome measure was time to azoospermia. Additional outcome measures were time to severe oligozoospermia (<100 000 sperm/mL) and vasectomy failure based on semen analyses.ResultsWe halted recruitment after the planned interim analysis, when 841 men had been enrolled. Fascial interposition decreased time to azoospermia (hazard ratio [HR], 1.35; P < 0.0001) and time to severe oligozoospermia (HR, 1.32; P < 0.0001) and reduced failures based on semen analysis by about half, from 12.7% (95% confidence interval [CI], 9.7 to 16.3) to 5.9% (95% CI, 3.8 to 8.6) (P < 0.0001). Older men benefited less from fascial interposition than younger men in terms of the speed of achieving azoospermia. However, the number of vasectomy failures was reduced to a similar degree in all age groups. Slightly more adverse events occurred in the fascial interposition group, but the difference was not significant. These failure rates may appear high to practitioners in countries such as the USA, but they are similar to results from other careful studies of ligation and excision techniques.ConclusionFascial interposition significantly improves vasectomy success when ligation and excision is the method of vas occlusion. A limitation of this study is that the correlation between postvasectomy sperm concentrations and risk of pregnancy is not well quantified.

Vasectomy surgical techniques in South and South East Asia

BackgroundSimple ligation of the vas with suture material and excision of a small vas segment is believed to be the most common vasectomy occlusion technique performed in low-resource settings. Ligation and excision (LE) is associated with a risk of occlusion and contraceptive failure which can be reduced by performing fascial interposition (FI) along with LE. Combining FI with intra luminal thermal cautery could be even more effective. The objective of this study was to determine the surgical vasectomy techniques currently used in five Asian countries and to evaluate the facilitating and limiting factors to introduction and assessment of FI and thermal cautery in these countries.MethodsBetween December 2003 and February 2004, 3 to 6 major vasectomy centers from Cambodia, Thailand, India, Nepal, and Bangladesh were visited and interviews with 5 to 11 key informants in each country were conducted. Vasectomy techniques performed in each center were observed. Vasectomy techniques using hand-held, battery-driven cautery devices and FI were demonstrated and performed under supervision by local providers. Information about interest and open-mindedness regarding the use of thermal cautery and/or FI was gathered.ResultsThe use of vasectomy was marginal in Thailand and Cambodia. In India, Nepal, and Bangladesh, vasectomy was supported by national reproductive health programs. Most vasectomies were performed using the No-Scalpel Vasectomy (NSV) technique and simple LE. The addition of FI to LE, although largely known, was seldom performed. The main reasons reported were: 1) insufficient surgical skills, 2) time needed to perform the technique, and 3) technique not being mandatory according to country standards. Thermal cautery devices for vasectomy were not available in any selected countries. Pilot hands-on assessment showed that the technique could be safely and effectively performed by Asian providers. However, in addition to provision of supplies, introducing cautery with FI could be associated with the same barriers encountered when introducing FI in combination with LE.ConclusionFurther studies assessing the effectiveness, safety, and feasibility of implementation are needed before thermal cautery combined with FI is introduced in Asia on a large scale. Until thermal cautery is introduced in a country, vasectomy providers should practice LE with FI to maximize effectiveness of vasectomy procedure.

Proper surgical training and grading of complications for shang ring circumcision are necessary

To the Editors: We read with some concern the recent article by Kanyago et al, entitled “Shang Ring versus forceps-guided adult male circumcision: a randomized controlled effectiveness study in southwestern Uganda.” Our Shang Ring study groups strongly believe in the need for highquality surgical training to decrease the number of postoperative complications, particularly with a new surgical device. It seems that although the surgeon in the study had performed more than 100 forceps-guided circumcisions, the article does not report any hands-on surgical training with the Shang Ring. Moreover, it is unclear why all ring sizes were not available for the study. The authors neither reference nor compare their experience with previous trials in Africa that demonstrated the safety of the Shang Ring. None of these trials observed the relatively high complication rates reported in this study. Also, the small study was underpowered to show differences in the primary end point. We note that there was a 25% loss to follow-up in the group of patients undergoing forceps-guided circumcision, versus 0% for the Shang Ring group, which raises the possibility of significant selection bias. The authors assumed that the 25% of patients lost to follow-up in the conventional circumcision group were “healed on the day of their next scheduled follow-up appointment,” for example, a patient presenting for a day 3 visit but not for subsequent appointments was considered healed on study day 7, an unlikely scenario for conventional circumcision. The authors in addition assumed that no complications occurred in this group of patients, which is surprising given that their complication rate in the forceps-guided group was a relatively high 18% in the intention-to-treat analysis. This for example is in contrast to the 0.8% moderate/severe complication rate for dorsal slit circumcision versus 1.8% for Shang Ring circumcision (P = 0.697) as reported by Kigozi et al. The 32% infection rate reported with Shang Ring circumcision in this study far exceeds the rates in all other Shang Ring studies and suggests (1) inappropriate surgical technique, (2) inaccurate diagnosis, or (3) lack of experience with Shang Ring wound healing. We are also puzzled by the 12.3% of men classified as “healed” at the 7-day visit for Shang Ring removal and the 34.3% healed by day 14. This is inconsistent with the detailed study by Barone et al, which reported the earliest complete wound healing was 21 days. We also question the definition of “persistent wound” as a complication of the procedure. Indeed, it is unclear how 30% patients undergoing Shang Ring circumcision could be listed as having a persistent wound versus 8% in the forcepsguided group, when the time to complete healing was similar in both groups (P = 0.08). Despite these concerns, it is gratifying to see that Shang Ring circumcision was nevertheless faster to perform and allowed patients to resume normal activity more quickly compared with the forceps-guided group, while maintaining at least an equivalent major complication rate and greater patient satisfaction. This article highlights the need for proper surgical training and an understanding of the wound healing process so as to avoid misclassification of complications for a device that could potentially increase the efficiency of surgery essential to the scale up of adult circumcision services in Africa.

A simpler tool for estimation of HIV incidence from cross-sectional, age-specific prevalence data

Background HIV incidence estimates are crucial in understanding and predicting the HIV/AIDS epidemic and identifying sub-populations and regions most at risk for the epidemic. However, incidence estimation is a challenge due to the nature of the disease and type of data available. This paper aims to present a simple and creative HIV incidence estimation method for resource constrained settings with scarce data. Methods The authors developed a simple user-friendly non-iterative spreadsheet estimation method, which can produce incidence estimates by age group using observed cross-sectional, age-specific HIV prevalence. Data from two prospective FHI microbicide Phase III clinical trials in Nigeria were used to validate the spreadsheet method. Since both the clinical trials involved condom use promotion to reduce HIV risk, the authors also used the AVERT software to estimate the extent of incidence reduction due to the intervention. Results The spreadsheet incidence estimates after accounting for AVERT adjusted reductions, for age groups 18–20, 21–25 and 26–30 were: 1.69%, 0.96% and 1.12% in the SAVVY trial, and 2.11%, 1.47% and 1.28% in the CS trial respectively. The corresponding actual observed incidence rates were 1.62%, 2.39%, and 1.13% in the SAVVY trial and 1.93%, 1.78% and 1.40% in the CS trial. Conclusion Comparisons of the spreadsheet-estimated incidence with the actual incidence from the clinical trials demonstrated that the method is reasonably accurate in its estimation. Because of the methods limitations it should not be used to evaluate HIV/AIDS prevention interventions or without understanding the direction of the bias in the case of an evolving HIV epidemic.

Minimally invasive male circumcision.

1. Sayana S, Javanbakht M, Weinstein M, Khanlou H. Clinical impact and cost of laboratory monitoring need review even in resource-rich setting. J Acquir Immune Defic Syndr. 2011;56:e97–e98. 2. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Department of Health and Human Services; 2011:1–167 Available at: http: //www.aidsinfo.nih.gov/ContentFiles/Adultand AdolescentGL.pdf. Accessed January 11, 2011.

Can therapeutic ultrasound be used as a reversible male contraceptive

Background, Motivation and Objective: Studies on the utility of ultrasound as a reversible male contraceptive were initially reported in the 1970s by Fahim and his colleagues. Their studies with rat and human subjects showed that a single dose of ultrasound could dramatically decrease sperm count and induced infertility for up to six months. Depending upon the dose of ultrasound, this contraceptive effect was reversible. Our objective was to determine if modern therapeutic ultrasound instruments could form the basis for a male contraceptive, and to elucidate acoustic mechanism of observed infertility. Statement of Contribution/Methods: In order to determine effect of ultrasound on reproductive capacity in-vivo, rat testes were subjected to 2.2 W/cm2 ultrasound at either 1 or 3 MHz using a therapeutic ultrasound generator and transducer. Testis histology and sperm counts were examined two weeks after treatment. To elucidate mechanism of ultrasound effects on reproductive cells, sperm from rat epididymis were sonicated in-vitro in a dual optical-acoustic-focus setup with 1 MHz pulses with lengths ranging from 1,000 to 10,000 cycles. Pulses had peak negative pressures between ∼1 and 10 MPa and were delivered at a 1 Hz PRF for between 30 and 90 s. Results: Sham-treated rats produced sperm counts between 200 to 300 million sperm per cauda epididymis, while ultrasound treatment reduced sperm counts to ∼2 million sperm per cauda epididymis two weeks after treatment. Sperm recovered from ultrasound-treated rats had reduced motility. The corpus and caput epididymis of treated animals had significantly lower numbers of sperm than sham-treated animals. In addition, portions of the epididymis had decreased tubular diameters, similar to that seen in castrated animals. The height of the seminiferous epithelium in ultrasound-treated rats decreased significantly compared to sham-treated animals, due to a significant loss of testicular germ cells. Individual sperm exposed to ultrasound ex-vivo were observed to be extremely resistant to acoustic energy. In-vitro sonication of sperm up to ∼ 10 Megapascals at 1 MHz did not permanently alter their motility after pulses were delivered. However, if microbubbles were present in the solution, cavitation caused permanent and terminal disruption of the cells within the field of view. Discussion and Conclusions: Our studies using modern therapeutic ultrasound instrumentation demonstrate the feasibility of using ultrasound as a form of male contraception. However, in-vitro studies have not yet elucidated the mechanism of cell disruption. Further studies determining the kinetics of germ cell loss, direct effects on sperm, the duration of the contraceptive effect, and any long-term effects to the seminiferous, interstitial or epididymal epithelia are needed to establish the efficacy and reversibility of any ultrasound-based contraceptive.