Male Circumcision: A possibility to reduce HIV infections?

As male circumcision is associated with reduced risk of sexually transmitted infections (STIs) many epidemiologists and researches take it as a main subject to effect HIV infections. Nevertheless still evidence for such protection is seemingly uncertain. The goal of this paper is to review systematically the verification for an association between male circumcision and a reductive effect on HIV infections. What exactly is male circumcision? Male circumcision is one of the oldest surgical procedures and due to their religios practice universal among Muslim, Jews and other ethnic groups in sub-Saharan Africa [Weiss]. Circumcision status and practices are characteristically assigned by culture, ethnicity and religion. Moreover circumcision bears different kind of risks if it is not performed under adequate hygienic conditions. Hence, circumcision should be performed by qualified individuals under high sanitary standards to avoid severe, immediate and long-term complications or even death. By an effective training of health professionals to perform safe mal circumcisions the post-operative complication rate levelled off at 0.2-2% [18]. In the medical definition it is the surgical removal of some or all of the foreskin (or prepuce) from the penis [2]. In the late 19th century physicians endorsed the preventing impact of circumcision in the United Kingdom, which was apparently proved by the lower disease prevalence among jewish people. [29] The neonatal male circumcision became a more and more common surgical routine in several parts of the US [9], Canada [33] in the mid-20th century, but the score fell proportionally with the number of announcements given by medical organisations confirming that their is no obvious indication for the neonatal intervention [9]. Nonetheless there are many reports discovering a potential association between male circumcision and sexually transmitted infections (STIs). A study published in 1855 arrived at this conclusion by comparing 61% of non-Jewish with 19% of Jewish suffering from syphilis[15]. Other studies emphasized this argument by presenting high proportions of uncircumcised men suffering from series of gential diseases like genital herpes [23], syphilis [33, 12] gonorrhoea [33,12] and chancroid [3, 12, 33, 2721, 10]

How can circumcision prevent HIV infections? According to the biological approach the histological statement results in a minor keratinization (deposition of fibrous protein) of the inner mucosa of the foreskin compared to the dry external skin surface. Therefore the tissue of the internal foreskin incorporates HIV approximately nine times more effectively than female cervical tissue, primarily due to the highter density of Langerhans and other HIV target cells than the cervix or other genital tissue (including other parts of the penis) [24]. Still researchers are in controversy about the keratinisation of the glans epithelium. As some authors deny a keratinised epithelium [15] others see no difference in the state of keratinisation between circumcised and uncircumcised men[30]. Due to the greater susceptibility to traumatic epithelial disruptions during intercourse the foreskin acts as a gateway for pathogens including HIV [30]. Additionally the micro-environment between the unretracted foreskin and the glans is a great benefit for the virus survival and increase [1]. But the propagation that the preputial space is more likely to accomodate sexually transmitted viruses (19) has been confuted by recent studies presenting genital warts are more widespread in the circumcised male (8) The declaration that the preputial mucosa represents a high density of Langerhans cells, which are charged with the crime to be the port of entry for HIV and other viruses, is based mainly on published paper advocating mass circumcision. Thus,
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profound studies on the density of Langerhans cells in the preputial mucosa of sexually active men with and without STDs is needed to facilitate a determination of the importance of this factor(32)Furthermore a wide exploration on the importance of inflammatory T-cells as a vehicle for HIV to enter Langerhans cells needs also to be clarified to determine the impact of predisposing infections as a necessary condition for HIV infection (26). On the contrary, others authors argue HIV would largely infect macrophages, CD4+ lymphoctes and other dendritic cells, but definetly not the epithelial cells [27] The pathogenesis is described as a passively binding of HIV to the dendritic cell surface, delivering the virus to receptive CD4+ T-Helper lymphoctes [23] To sum up the pros and cons, circumcision may hence diminish the risk of HIV infection following two directions. First, the total absence of foreskin may concretely reduce the risk of HIV infection by detaching a rich source of HIV supporting cells and second, by removing

a working surface for ulcerative STIs, as lesions promote a better susceptibility for HIV by demolishing the integrity of the mucosa and therefore increase the accessibility of local macrophages and lymphocytes by evoking immunal and inflammatory response[Weiss]. Several studies explored the possibility of an association between male circumcision and chancroid (12,28, 6, 17, 20, 14,7). Six out of seven trials noted a reducing effect to chancroid among circumcised men, which became highly statistically significant in four trials. But no meta-analysis was carried out for these studies due to the circumstance that the ascertainment of the outcome differed between trials and, however, the control groups varied considerably by including men with other STIs (e.g. urethritis)(30,22) The single study with a focus on a serological performance obtained results emphasizing no association with circumcision (32) Another fourteen studies tried to discover a potential association between male circumcision and a reduced risk to serological evidence of syphilis infection, whereas five of them showed statistically significant reduced risk. In fact, circumcisions are not standardized, therefore the quantity of foreskin left after circumcision is very variable, ranging from a total removal up to parts of foreskin being mostly still present. Ppin et al. assumes that HIV infections are seemingly to be more common among functionally uncircumcised although they have undergone ritual circumcision (25). In addition, the meta-analysis by Hayes et al. stated that the studies made no differentiation between total and partial removal of the foreskin, which gives rise to a non-substantive evidence concerning male circumcision as prevention against HIV infections. Unfortunately the link between the capacity of penile hygiene as a defensive against HIV infection or other sexually transmitted infections is insufficiently reported by studies of the pre-antibiotic era, when people were trying to prevent chancroid with the simple use of soap and water [5] The personal hygiene is reported to be the motivation for circumcision, whereas among several tribes in Kenya circumcised men are perceived to be cleaner and, thus, more attractive sexual partners (33) The first randomized clinical trial, the so called orange Farm Study, assessing the preventive impact of male circumcision against HIV infection published in 2005 evaluated more than 3000 HIV negative men. The ANRS (French Agence Nationale de Recherches sur le Sida) team of French and South African researchers demonstrated that circumcision reduced the risk of HIV by 60 percent [Orange Farm

Study]. Several Researchers have observed among the African and Asian population significant variations in HIV prevalence that may be associated to levels of male circumcision in the community. Obviously HIV prevalence is lower in areas where circumcision is common and areas of high HIV prevalence seem to overlap with low rate of male circumcision [4]. Another two randomized trials involved HIV-negative heterosexual male volunteers assigning to circumcision or no circumcision, who intended to stay near the study site for the trial duration. Both studies took place in Kenya and Uganda, counselling all participants extensively counselled in HIV prevention and risk reducing techniques[15a, 34].

Circumcision as public health intervention? There is a slight evidence that in some parts of East and South Africa, where male circumcision is referred to be a traditional and religious routine, the overall preference for this intervention may be increasing (13) A trial focussing the convenience had an outcome of 216 volunteers being surveyed, whereas 60 % of men would prefer to undergo circumcision, while 62 % of women would favour their sexual partner to be circumcised.(11) Regarding the acceptability of male circumcision, some important parameters can be noted. First social, cultural and religious beliefs concerning male circumcision have to be attended. The perceived health or social benefits due to the surgical intervention are secondly of high interest. Furthermore there is an interest in the procedures safety and also in a rate for complications and side effects. On the other hand acceptability depends on the level of perceived pain and discomfort associated with male circumcision and, finally on the resulting cost. These determinants are particularly of high relevance where male circumcision is intended to be introduced as a public health mass intervention in a formerly noncircumcising community. The potential stigmatization of voluntary circumcised individuals in a common non-circumcised population may be bypassed by obtaining a certain amount of community acceptability. Conversely, there is unreliable indication for a considerable quantity of peer pressure in several circumcising communities for men to be circumcised. Male circumcision may be introduced as a public health intervention by establishing it as an alternative to the ceremonial circumcisions, most of men try to avoid (6)

Moreover, the acceptability of male circumcision among health care delivery system may persuade to discuss the preventive impact of male circumcision on HIV infections on higher levels. Aside from the acceptability there is a need to aspect the effect of circumcision at different ages. The median age of circumcision oscillates at 18 in Kenya, while ranging from 12 to 22, and the age appears seemingly to rise slowly. Apparently circumcision offers the same effects with regard to the prevention of HIV infection, regardless of the age of performance. Therefore the most preventing effect circumcision may release by a performance of intervention before or soon after onset of puberty (16) Another effects of male circumcision are gender-related implications, whereas male circumcision may offer an immediate benefit to HIV-seronegative men, but also it may have a positive impact on the transmission of HIV to women as circumcised HIV positive men demonstrated lower HIV loads (<50000c/ml)(5) In terms of public health infrastructure, the feasibility of male circumcision is defined by the range of available resources, trained and equipped staff and cost associated commodities for the intervention. To establish a safe male circumcision standardized program, appropriate education and proper guidance in techniques are required and, moreover, the availability of adequate surgical instruments, as resources vary from one to another country. Regarding the impact on economy, the direct costs (training of staff, providing health care with facilities and necessary surgical equipment, evaluation program) and the opportunity costs (public health programs, other prevention activities that are replaced by intervention) have to be considered. As in some communities the male circumcision is anecdotal called an invisibe condom a mass intervention my increase risk behaviour, including reductions in condom use. Thus, this will probably put women at high risk of HIV infection, while it may reciprocally reduce the potential benefit of male circumcision on HIV transmission. The embedded suggestion points out a cautious approach to implement male circumcision as public health intervention and, however, to improve accompanied HIV preventing health training, education classes for safe sexual practices, counselling and change interventions on common sexual behaviour with the goal of promoting condom use.

Conclusion Many studies emphasize the benefitial impact of male circumcision, but despite considerable evidence there are notable concerns about the randomized studies in the African communities. But with most prevention strategies, adult male circumcision is not completely effective at preventing HIV transmission without supporting preventive strategies to alter the common sexual behaviour. Before implementing circumcision as optional, circumcised men who perceive to be at decreased risk for transmission and, thus, may not maintain other risk reduction strategies, should be absorbed by evaluation. Modest inclinations in the amount of sexual partners may reverse the protective effect and give rise to a higher rate of HIV transmission in a community. Hence, adult male circumcision might be most efficient being integrated into an extensive prevention strategy including the ABC (Abstinence, Be Faithful, and Condoms) of HIV prevention. To give sound response to all the concerns above, randomized controlled studies should ideally be improved in method and strategy to study other determinants on HIV transmission. Nevertheless, randomized control trials should likely be conducted among men with potential high risk, where they might be more feasible. As there is still not enough knowledge about the association between age at circumcision and risk of HIV infection, more trials regarding this subject should be performed. Hence, there is a need for more data respective the impact of male circumcision on male and female risk behaviour, their behavioural alternations regarding condom use, sexual practice and sexual hygiene. To grasp all the beneficial effects by introducing a male circumcision program further knowledge how to guarantee standards of the surgical intervention and quality assessment is needed. Consequently, to state recommendations on male circumcision in current trials regarding the impact on non-circumcising communities, more research on male circumcision in populations practicing circumcision as a ritual routine, is required. Acceptability trials and the examination of feasibility for rapid assessment tools should be improved to estimate costs of male circumcision interventions by developing operations to conduct preparations for possible male circumcision programs.

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