Sexual health

Female sexual arousal disorders constitute a varied spectrum of difficulties, ranging from the total absence of genital or subjective pleasurable arousal to feelings of persistent genital arousal in the absence of sexual desire. Arousal disorders can be associated with physical factors (eg, vaginal dryness) or psychological factors (eg, anxiety, distraction), or a combination of both. The most common complaint is the absence of subjective sexual excitement or pleasure despite adequate physical arousal (eg, lubrication). Pharmacological and physical treatments include the use of oestrogen, lubricants and vibrators. There may be a place for drugs that increase vasocongestion and vasodilation. Psychological therapy addresses inhibitions, and interpersonal and motivational factors.

Sandra R Leiblum PhD

In consultations with older women, doctors should ask about sexual problems. A holistic approach is needed to examine the many different factors that can affect sexuality. Hormonal changes associated with ageing have an impact on women's sexuality. Doctors need to have a clear idea of the place of hormonal treatment for different sexual problems. Physical changes associated with ageing, including illness and disability, may interfere with sexual expression. Diseases of the endocrine, vascular and nervous systems will most commonly affect sexual function. A broad range of psychosocial factors associated with ageing may influence sexuality.

Lesley A Yee MB BS(Hons), MM(Psych) · Kendra J Sundquist EdD, MHlth, Sc(Ed)

Health inequalities exist for lesbian and bisexual women, largely related to experiences of discrimination, homophobia and heterosexism. These issues can lead to avoidance of routine healthcare and screening and reduced disclosure of sexual orientation within consultations. Lesbian and bisexual women have specific healthcare needs in areas of sexual and cervical health, reproductive health and parenting, mental health, substance use, and ageing. Facilitation of disclosure of sexual orientation, identity and behaviour within the consultation is desired by most lesbians and important for addressing specific health needs. Healthcare providers should develop "cultural competence" in lesbian issues to enhance their care of lesbian and bisexual women. Healthcare providers have a role in promoting awareness of lesbian health issues and inequalities in the arenas of healthcare provider education, research and health policy.

Ruth P McNair MB BS, DRACOG, DA

Vaccination has the potential to reduce the global burden of disease from genital HPV infection Cervical cancer is the third most common cancer worldwide and, for women, the second most common after breast cancer. Each year there are about 466 000 new cases globally, and around 232 000 women die of cervical cancer.1 Eighty per cent of cases occur in developing countries, where it is the leading cause of cancer-related death among women.1 Precursor lesions (high-grade dysplasias) precede the development of cancer by years. With appropriate screening programs and early diagnosis and treatment, this reproductive health problem becomes a preventable public health issue. However, data for the past 5 years indicate that only about 5% of women in developing countries are screened, compared with 40%–50% of women in developed countries. Further, because of the insensitivity of the Papanicolaou (Pap) test, even in countries with appropriate screening programs, 50% of adenocarcinomas and at least 25% of squamous cell carcinomas occur in adequately screened women. Association between human papillomavirus and cervical cancerMolecular biology has finally established the causal association between persistent infection with certain human papillomavirus (HPV) genotypes and cervical cancer, supporting previous observations relating cervical cancer to sexual activity.2-4 HPV genotypes 16 and 18 are now categorised as human carcinogens,2 and it is noteworthy that these two HPVs are present in over 70% of cases of cervical cancer worldwide.2-4 Further, in a study of almost 1000 cervical cancer cases worldwide, the prevalence of HPV infection was 99.7%.3 Recently, less prevalent oncogenic HPV genotypes (31, 33, 45, 52, 58, 59) have also been found to be strongly associated with cervical cancer, with odds ratios several hundredfold.4 With such high relative risks, the association between persistent oncogenic HPVs and cervical cancer is the strongest for any environmental factor and human cancer. From recently completed longitudinal studies, we now know that genital HPVs are the commonest sexually transmitted viral infection. They are largely transient, usually asymptomatic and most are of no clinical consequence. The mean duration of carriage is 4 months for low-risk oncogenic types and 8 months for high-risk oncogenic types, with HPV-16 carriage being even longer.5 Genital warts are caused by genotypes 6 and 11 (low-risk HPVs), while persistent infection with oncogenic genotypes (over years and in a minority of patients) results in severe dysplasia or, ultimately, carcinogenesis. This process involves other cofactors (host and/or exogenous factors, such as high parity, cigarette smoking) and complex pathways, which are not completely understood. HPV DNA as a marker for precursor lesionsPersistent infection with oncogenic HPVs precedes virtually all high-grade dysplasias or neoplasias. Thus, persistent positivity for high-risk HPV DNA is a marker for current or subsequent development of precursor lesions,5 with persistent HPV DNA type-specificity being an even stronger predictive factor.6 Cohort analyses show that negative baseline Pap and HPV DNA tests are associated with very low risks of high-grade disease (0.16%). By comparison, women with positive HPV DNA tests and abnormal Pap smear results have a 4.54% cumulative incidence of high-grade dysplasia or cancer.7 HPV DNA testing, with its higher sensitivity for detecting underlying high-grade lesions than the Pap test (and the advantage that it can be performed on self-collected samples), is being reviewed for its clinical utility, either in triage of inconclusive or minimally abnormal smears, in conjunction with the Pap test, or as a stand-alone test in primary screening.5 It may also have a role as a test of cure after ablation for cervical dysplasia; persistence of HPV DNA after treatment could be an accurate predictor of residual disease or relapse.5 Of note, in the United States, HPV DNA (Hybrid Capture 2) testing was recently approved for use with the Pap test for women 30 years and over.8 Vaccination prevention at last?The preliminary results of a recent trial of a monovalent HPV genotype 16 vaccine were received with great interest and enthusiasm (Box). The vaccine provided vaccinees with high-level protection for incident and persistent HPV-16 infection (as a surrogate for invasive cancer) and HPV-16-related cervical intraepithelial neoplasia (CIN).9 Now awaited are larger studies to prove that clinical disease is prevented by vaccination, and the results of current clinical trials evaluating multivalent vaccines (HPV types 6, 11, 16 and 18). If these vaccines are as successful as the interim monovalent vaccine,9 they have the potential to prevent genital warts and over 70% of dysplasias and cancers, as well as reduce the occurrence of abnormal Pap smear results and the costs of their follow-up and management. Pivotal in the development of these vaccines was the production of virus-like particles (VLPs) — an Australian first.10 The VLPs used for the HPV-16 vaccine are viral subunits, composed of the major capsid protein L1 or outer shell of HPVs. Being devoid of DNA, they are not infectious. In Phase 1 and 2 clinical trials, VLPs have been shown to be not only immunogenic and safe, but able to induce strong cell-mediated and humoral immune responses. Most encouraging is that VLPs produce neutralising antibodies in animal models that are protective against challenge as well as long lasting. We need to see whether VLPs induce similar long-lasting immunity in humans. Second-generation vaccinesSecond-generation vaccines will need to be easier and cheaper to develop, give a broader coverage, have a better delivery system, allow better mucosal delivery, and possibly incorporate both prophylactic and therapeutic cover. The initiatives of the Gates Foundation to reduce cervical cancer in developing countries, where the disease is most common, are to be commended.11 Initiatives to promote second-generation vaccines (eg, vaccines that are cheaper to manufacture and available in a non-injectable form) have been discussed at a meeting of HPV vaccine experts, convened by the Gates Foundation in Seattle, Washington, in September 2002. Therapeutic vaccines have been successful in animal models, and there have been various Phase I and II trials in humans using HPV subunits (modified fragments of the HPV E6 and E7 genes), as well as chimeric and DNA viral approaches.12 These trials have shown some encouraging results for intraepithelial neoplasias, although clinical trials are not as advanced as for the prophylactic vaccines. An important question for vaccine development is whether there will be any cross-protection between types (immunity induced by natural infection is type specific), or whether effective vaccine-induced immune responses to one common high-risk HPV might simply open the door to another, currently less common type. In Australia, mortality from cervical cancer has been reduced substantially by an effective Pap screening program, but this comes at a considerable cost, both to the health budget and to women who face the psychological impact of having an abnormal Pap smear result. Ultimately, successful vaccination has the greatest potential to reduce the global burden of disease from genital HPV infection. Development of a vaccine for a sexually transmitted infection, the infective agent of which can not be grown by traditional methods in the laboratory, could be seen as a very important breakthrough, particularly for Australia (as VLPs were developed here).10 An effective prophylactic vaccine could ultimately obviate the need for population-based Pap smears, while an effective therapeutic vaccine could provide a change to conventional management of cervical disease, including reducing the need for colposcopy. However, lowering the incidence of dysplasia and neoplasia will take many years. In the meantime, the various prevention strategies still need to be endorsed and maintained. Apart from cervical cancer, other anogenital cancers and some non-melanoma skin cancers are also attributed to oncogenic HPVs. A successful vaccine could ultimately have an even greater impact on HPV-related diseases. Other challengesBesides vaccine delivery, vaccine implementation would include educating the general public about HPV (public awareness and acceptance), de-stigmatising HPV infection, and gaining acceptance for vaccinating adolescents (or pre-adolescents), possibly of both sexes, for a sexually transmitted infection before their sexual début. For the future, we need a better understanding of the transmission dynamics of HPV. A public health policy will need to be guided by mathematical modelling of the impact of an HPV vaccine on Pap screening. This also applies to the interrelationship between HPV and abnormal Pap smear results, and any concomitant psychological impact on women faced with an abnormal result of an HPV DNA test or a Pap smear. A controlled trial of a human papillomavirus (HPV) type 16 vaccine, by Koutsky et al9 Study population: 2392 young women, 16–23 years old (no more than five male sexual partners during their lifetime). Intervention: Intramuscular vaccination with three doses of placebo or HPV-16 virus-like particle (VLP) vaccine (Day 0, Month 2, Month 6). Follow-up: Month 7, 12 and thereafter 6 monthly to 48 months (Pap test, and HPV DNA 16 and HPV-16 antibody assayed). Colposcopy biopsy tissue evaluated for cervical intraepithelial neoplasia (CIN). Primary endpoints: Persistent HPV-16 infection (the detection of HPV-16 DNA in samples obtained at two or more visits ≥ 4 months apart, in those HPV DNA negative at Day 0 and Month 7) and HPV-16-related CIN. Results: After a median follow-up of 17.4 months, the incidence of persistent HPV-16 infection was 3.8/100 woman-years (placebo group) and 0/100 woman-years (vaccine group) (100% efficacy; 95% CI, 90–100; P < 0.001). Nine cases of HPV-16-related CIN occurred, all in the placebo group. 99.7% of the women vaccinated seroconverted and with a robust antibody response. Conclusion: HPV-16 vaccine reduced the incidence of both HPV-16 infection and HPV-16-related CIN. The study is continuing.

Suzanne M Garland FRCPA, FACSHP, RANZCOG ad eund, MD

Cervical screening in Australia is a successful public health initiative. Since the introduction of the National Cervical Screening Program in 1991, there has been a significant fall in incidence of and mortality from cervical cancer. Laboratory quality procedures are critical to ensuring optimal outcomes. Laboratory accreditation procedures are being reviewed in line with recent government recommendations. For a sustainable program, cost-containment issues need to be considered; screening interval, management of screen-detected abnormalities, and new technologies are the critical drivers of cost.

Annabelle Farnsworth FRCPA, FIAC · Heather S Mitchell FRACP, FAFPHM

To the Editor: Spilsbury et al argue that "improved education for physicians, and perhaps parents, with regard to foreskin development and management is required."1 However, updating of textbooks and medical curricula is required to accomplish this objective. Articles by Caldamone et al2 and Cendron et al3 are two examples of incorrect data in text books. Gairdner was the first to provide data on the normal development ...

George Hill

To the Editor: The study by Spilsbury and colleagues provides new data on rates of phimosis, balanoposthitis, and lichen sclerosus.1 However, it does cite sources — Øster2 and Shankar and Rickwood3 — that indicate very low rates of phimosis. Øster was a school medical officer who followed up his subjects for several years, making frequent penile inspections and giving them continual instruction on prepuce care. ...

Stefan A Bailis

To the Editor: In the recent article by Spilsbury and her colleagues on circumcision for phimosis, a key part of their argument hinged on probable rates of phimosis among boys.1 I take no stance for or against circumcision, but I have published on evolutionary aspects of the human foreskin and the origins of circumcision,2 for which I surveyed the literature on the occurrence of phimosis. Spilsbury ...

Guy Cox

To the Editor: The article by Spilsbury et al starts well by acknowledging at least some of the serious health consequences of not circumcising,1 but then digresses into a study of whether a particular medical reason for circumcision — namely phimosis early in life — has been overstated in medical records. So what! Circumcision is a simple procedure that conveys significant lifetime health benefits. Like immunisation, ...

Brian J Morris

In reply: We support Hill in his call for improving the dissemination of information and data about foreskin development and management. Circumcision is a highly emotive issue. Our study on phimosis1 was carried out under the Western Australian Safety and Quality of Surgical Care Project, established in 1996, to assess the safety, quality, appropriateness and outcomes of surgical care in the state. The purpose of our ...

James B Semmens

To the Editor: Chlamydial infection is the most common bacterial sexually transmitted infection in Victoria and Australia, and notifications are increasing significantly. Most chlamydial infections are asymptomatic and, if untreated, lead to significant morbidity.1 The direct costs of these infections to the Australian healthcare system have been estimated at $90–$160 million annually.2 Chlamydial infection has been implicated in as many as 50% of cases of infertility.3 Widespread screening is cost effective and reduces both the prevalence of infection and the rate of complications.4 Screening is recommended in a number of countries and in the recently released Victorian Chlamydia Strategy.2 To determine if there has been an increase in the proportion of women tested for chlamydial infection who are asymptomatic in Victoria, we analysed notification and enhanced surveillance data. Since 1997, the Department of Human Services has collected enhanced surveillance data using a standard questionnaire distributed by laboratories to clinicians. The forms record information on risk factors and the reason for testing. Data from the Health Insurance Commission were obtained to provide an indication of trends in testing through Medicare. The number of notifications almost doubled between 1997 and 2001, from 2059 to 3977 notifications (Box). In 2001, enhanced surveillance data were available on 2300 notifications (58%). Symptomatic presentation remained the major reason for testing (53%), with no significant change in the proportion tested for this reason since 1997. However, when data for the two sexes were analysed separately, the proportion of men who were symptomatic fell significantly between 1997 and 2001, from 77% to 65% (P = 0.02), while there was no change in the proportion of women who were symptomatic — 42% in 1997 and 41% in 2001 (P = 0.35) (Box). From 1997 to 2001, the number of positive chlamydial tests notified relative to the number of tests conducted has remained constant (9.7%, 8.8%, 11.8%, 11.5% and 9.8% in consecutive years, respectively), despite the increase in number of tests performed. However, even if all tests had been performed in the 20–30-year-old age group, they would represent only 10% of the population in that age group tested each year. Our data suggest that the reasons for testing over the past 5 years have not changed, and, in particular, that there has been no change in the proportion of women tested who are asymptomatic. Chlamydial infection meets the World Health Organization criteria for a screening program,5 and screening for this infection is cost effective.4 Although chlamydial infections are a significant public health concern for women, targeted screening is not occurring widely. Chlamydia notifications and enhanced surveillance data for Victoria, 1997–2001 1997 1998 1999 2000 2001 Male Female Male Female Male Female Male Female Male Female Number of notifications 788 1271 948 1542 1181 1761 1328 1915 1631 2346 Number with enhanced surveillance data 484 782 619 954 735 968 858 1037 992 1308 Reasons for testing* Symptomatic 76.9% 42.3% 75.8% 46.0% 73.9% 44.1% 68.6% 39.4% 64.9% 41.1% STI Screen 7.2% 25.4% 6.5% 25.6% 9.0% 26.3% 9.8% 27.2% 12.3% 27.2% Asymptomatic contact 13.8% 15.5% 16.2% 17.5% 15.8% 18.7% 18.1% 16.9% 18.9% 17.4% Abnormal examination 0.2% 3.2% 0.6% 3.8% 0.7% 4.0% 0.2% 1.6% 0.8% 2.3% Pre-termination screen 0 9.3% 0 5.5% 0 5.6% 0 5.6% 0 3.7% Other/not stated 1.9% 4.3% 0.9% 1.7% 0.6% 1.2% 3.2% 9.3% 3.1% 8.4% Total notifications 2059 2490 2942 3243 3977 STI = sexually transmitted infection. * Mutually exclusive choices presented to clinicians in the surveillance questionnaire.

Megan L Counahan · Jane S Hocking · Christopher K Fairley

Community-based surveys indicate that about a fifth of women have significant vulval symptoms lasting over three months at some time in their lives. Common causes of itch or pain are dermatitis, recurrent candidiasis and the recently recognised pain syndromes — vulvar vestibular syndrome and dysaesthetic vulvodynia. Diagnosis is usually apparent after a thorough history and examination, although conditions commonly coexist and are complicated by prior treatment. Skin lesions not responding to treatment require biopsy. Treatment aims to control symptoms rather than to cure; avoiding soaps and other irritants is central to management. An early, accurate diagnosis should enhance management of vulval conditions, particularly pain syndromes.

Belinda M Welsh FACD · Karen N Berzins DRANZCOG, Dip Ven · Kathy A Cook FRACOG · Christopher K Fairley FRACP, PhD

Clinical record Day 1: A 32-year-old man who was HIV positive presented to a specialist HIV clinic with a one-month history of rectal discharge. Serological tests for syphilis performed five months earlier were unreactive. There were no genitourinary symptoms at this visit. Swabs to test for gonorrhoeal and chlamydial infection were obtained from the throat, urethra and rectum, and the patient was referred for serological tests for syphilis at a follow-up visit one week later (he was immune for hepatitis A and B). He had no penicillin allergy. He was given empirical treatment for chlamydia and gonorrhoea (a single dose of azithromycin 1 g orally and ceftriaxone 250 mg intramuscularly). His contacts were unknown. Six hours later the patient developed severe fever, chills, rigors, headache, severe myalgia and photophobia and was prostrate in bed overnight. Self-administered paracetamol did not relieve the symptoms, which largely subsided spontaneously after 8 hours. Day 2: The patient noticed a rash on the soles of his feet, and myalgia persisted, but his other systemic symptoms resolved. He contacted the clinic and was advised to return immediately for syphilis serological tests, as the acute symptoms suggested a Jarisch–Herxheimer reaction. On examination, the patient had bilateral non-tender inguinal lymphadenopathy. No chancres (ulcers of primary syphilis) were visible, including in the oral cavity and the perianal and genital areas. There was a non-pruritic, macular, symmetrical rash on the soles of both feet. His ankle joints were tender on passive movement. Day 3: Neisseria gonorrhoeae was isolated from the rectal culture. The serological tests for syphilis showed a rapid plasma reagin titre of 1:8 and a reactive Treponema pallidum haemagglutination assay. The patient's presentation was consistent with a Jarisch–Herxheimer reaction unmasking secondary syphilis (ie, systemic, cutaneous and nodal involvement, without a primary chancre). Subsequently, the patient was given 1.5 g procaine penicillin intramuscularly for 14 days. His sexual contacts were unknown. With continued treatment, his plantar rash became desquamating, and a new symmetrical macular rash appeared on his arms and trunk, but not on his palms. Follow-up: Over the next few weeks, the patient's symptoms resolved completely. Three months after treatment, his rapid plasma reagin titre had fallen to 1:4 and by 6 months it had fallen to 1:1. Classic presentation of secondary syphilis: macular, symmetrical rash on the back, palms, and soles. (NB: These photographs are not of the patient reported, who did not have a rash on his hands. However, the rashes he had on his back and feet were very similar to those shown.) In this patient, syphilis was unmasked by the Jarisch–Herxheimer reaction after ceftriaxone therapy for rectal gonorrhoea. The Jarisch–Herxheimer reaction is a self-limiting febrile reaction occurring 4–8 hours after penicillin treatment in 95% of early (primary and secondary) syphilis cases. The pathogenesis is unknown although lysis of the spirochaete, releasing endotoxin, probably contributes to the systemic illness. As the patient had no laboratory confirmation of syphilis at the time of presentation, we made this diagnosis based on (i) the acute onset and systemic nature of the symptoms of fever, malaise, chills, rigors, myalgia, and headache, occurring 6 hours after ceftriaxone injection; and (ii) the complete resolution of symptoms within 24 hours — all characteristic features of this reaction. Secondary syphilis occurs as the spirochaete disseminates from the site of infection (chancre) via blood and lymph nodes. A characteristic symmetrical macular rash (often on palms and soles) occurs 4–10 weeks after the appearance of the chancre. Less common symptoms include malaise, myalgia, pharyngitis, headache, lymphadenopathy, condylomata lata (which may mimic genital warts), oropharyngeal snail-track ulcers and, rarely, generalised pruritis. However, the diagnosis of secondary syphilis in this patient was clinical and based on (i) the Jarisch–Herxheimer reaction; and (ii) the appearance of the characteristic body and plantar rash (see Box), which intensified during treatment and desquamated before disappearing with successful treatment. Primary syphilis was excluded as there were no chancres. Because the systemic symptoms of the Jarisch–Herxheimer reaction and those of secondary syphilis are similar and overlap, delineating where the former "ends" and where the latter "starts" is not always clear-cut. The symptoms of secondary syphilis may increase during the Jarisch–Herxheimer reaction. The recommended treatment for early syphilis is 1 g procaine penicillin intramuscularly for 10 days.1 In our patient, the attending physician decided on a longer course and higher dose because the patient's HIV viral load was > 100 000 copies/mL and the CD4 count (350 × 106/L) was low. The efficacy of ceftriaxone in primary and secondary syphilis is comparable with that of intramuscular penicillin,2,3 and ceftriaxone is used in treating penicillin-allergic patients in the United States4 and Europe.5 One case of Jarisch–Herxheimer reaction after ceftriaxone therapy for primary syphilis has been reported;6 however, to the best of our knowledge, this adverse reaction to ceftriaxone has not previously been reported in Australia. The incidence of syphilis is increasing among homosexually active men in some large cities overseas (eg, Los Angeles).7 In south-eastern Sydney in 2002, 20 of the 119 notifications of syphilis received to August were classified as new infectious cases, compared with a total of 19 infectious syphilis cases notified for the whole of 2001.8 Local guidelines for sexual health testing have been established in response to concurrent gonorrhoea and hepatitis A epidemics in south-eastern Sydney.9 Screening for sexually transmitted infections is recommended at least annually among homosexually active men. All patients receiving intramuscular antibiotic treatment for early syphilis should be forewarned about the Jarisch–Herxheimer reaction. Without this reaction, syphilis may have been missed in this patient, had he not returned for serological tests a week later, as prearranged. Ideally, in this high-risk, symptomatic patient, serological tests for syphilis should also have been done at his initial presentation. In conclusion, the main lesson from this case is the need for full screening for sexually transmitted infections in all high-risk patients presenting with anogenital symptoms. Lessons from practice A thorough sexual history should be obtained from sexually active individuals at each visit to enable screening for sexually transmitted infections (STIs) and education to occur. Patients presenting with new symptoms suggestive of STIs should be screened for other STIs. Current guidelines recommend screening for syphilis and other STIs in sexually active individuals at least annually. In high-risk patients, more frequent screening should be considered. In Australia, intramuscular penicillin is recommended as first-line treatment for syphilis. All patients receiving intramuscular penicillin for early syphilis should be forewarned about the Jarisch–Herxheimer reaction.

Derek J Chan MB ChB, MM, MPH · Harry M Michelmore MB BS, DipVen, FACSHP · Julian Gold FACHSE, FAFPHM, MD

1: Clinical definition of adult male or female sexual assault6 a) Penetration of the vulva (beyond the labia majora) and/or anus by a penis or any other object, and/or penetration of the mouth by a penis and b) Without the consent of the person A United States meta-analysis estimates that 13% of women and 3% of men worldwide may be raped at some time during their lives.1 New Zealand and Australian data suggest similar findings,2 ranging from 4.6%3 to 11.3%4 in different populations. Although reliable incidence figures are impossible to estimate given considerable barriers to reporting,4 sexual assault presents, often unexpectedly, to healthcare providers working in diverse areas.5 Practitioners may feel sexual assault is challenging to manage, but it is simple when broken into components — emotional, physical and medicolegal. Here we provide a framework for non-forensic medical management of recent adult sexual assault. Box 1 gives a clinical definition, broader than that used in Australian law. DisclosureVictims are reluctant to disclose that they have been sexually assaulted for many reasons, including fear of police, not being believed or retribution, as well as guilt and a desire to forget the event. However, they may present for medical care because of concerns about pregnancy, sexually transmissible infections (STIs), or injury.7 They may present with post-traumatic stress, depressive symptoms,8 alcohol or substance misuse or self-harm.9 To encourage disclosure it is necessary to ask directly about the possibility of sexual assault. 2: Asking about sexual assault Have you ever been forced to have sex you didn't want? Have you ever had sex forced on you? Have you ever been sexually assaulted? Most victims of reported sexual assault are women; men are also assaulted, but are less likely to disclose.10 Although people of all ages and cultures are vulnerable, prisoners,11 adolescents, injecting drug users, the elderly, those who experienced sexual assault as children, and people with mental or physical disabilities are at particular risk.12 A recent survey of sexual health clinics in Australia and New Zealand found that staff were more likely to ask about sexual assault if their workplace encouraged it.13 It also identified patient distress, time constraints and lack of expertise in managing a positive response as barriers to asking. However, nearly all of the patients in the survey reported they did not mind being asked about sexual assault.13 A recent Sydney survey linked sexual assault firmly with the words "forced" and "non-consent" (L Dayan, Director, Sexual Health Services, Royal North Shore Hospital, Sydney, personal communication). Suggestions on how to ask about sexual assault are shown in Box 2. ManagementWhen responding to a disclosure of sexual assault, it is important to: ensure privacy, safety and adequate time for the victim; acknowledge their courage in speaking out; accept the victim's story in a non-judgemental way — it is the role of police to investigate story veracity; explain that reactions to rape, such as shock, arousal, anxiety and fear are normal, emphasising that the victim is not to blame; and understand that the aim of management is to return control to the victim by enabling them to make choices about reporting, counselling and medical therapy (see Box 3). Further action is defined by whether the victim decides to make a formal complaint. Most jurisdictions require that the first person who hears an allegation of sexual assault must give evidence if the complaint comes to trial, so document the exact words used, even if the victim is referred for forensic management. HistoryAssess any injuries and ongoing safety and support. Emergency accommodation may be needed if the victim's home is not safe. A brief history of when and where the assault took place, who put what where, and contraception or condom use will inform immediate treatment. Ask whether the victim wants to report the assault to the police. Early referral to a sexual assault service assists forensic testing. A forensic assessment involves careful documentation of injuries and testing for the presence of foreign DNA; the findings are compiled in a court medicolegal report. Even if the victim is unsure about wanting to report the assault, if there is any possibility of a complaint being made forensic assessment will preserve evidence in case a formal report is made to police at a later date. Ask about the possibility of drug-assisted rape, which is becoming increasingly common worldwide.14 Early forensic referral may facilitate detection of commonly used drugs (eg, flunitrazepam, ketamine) in the victim's blood or urine. Testing must be performed in a police laboratory to preserve continuity of court evidence. If the patient keeps a spot urine specimen, this can be handed directly to the police. ExaminationA thorough general and genital examination should be performed and any injuries documented. Although most sexual assault services use speculums for examining women, this depends on both the woman (comfort versus her need to know all is normal) and the practitioner (expertise and requirement for testing), and should be discussed with the woman before examination. Similarly, the use of a proctoscope may be required. Victims are often afraid that there has been genital damage which will make it obvious to others that they have been raped. Feedback that everything looks normal, as is usually the case,15 can be very reassuring. InvestigationTests for forensic purposes, sexually transmissible infections and pregnancy are performed according to need. If a woman is being transferred to a sexual assault service for forensic assessment after unprotected vaginal rape, the initial dose of the emergency contraceptive pill should be given first. Forensics: If the victim is willing for the police to be involved, he or she should be referred immediately to an expert sexual assault service for forensic assessment (a list is provided at the end of this article). If a victim is undecided about reporting the assault, forensic specimens may be stored while a formal complaint is considered. DNA evidence left on or in the body of a victim, particularly in moist areas, degrades quickly over 2–10 days.16,17 Therefore, forensic assessments need to be made as soon as possible, but within 10 days of an assault. If proceeding to a forensic assessment, advise victims not to shower (or to clean their teeth or rinse their mouths if the assault was oral), and ensure all clothes worn during the assault remain unwashed. As DNA evidence degrades quickly if moist, ask the victim to store underclothes worn during the assault in paper (not plastic) bags. In remote areas, timely expert forensic assessment is difficult. Most sexual assault services provide 24-hour phone assistance by doctors experienced in forensic medicine to discuss assessment. After discussion, some practitioners in remote areas may decide to perform forensic assessments, but this can be a difficult decision, as the practitioner may later be required to give evidence in court. Sexual assault services in Western Australia suggest a compromise solution that entails wiping the victim's vulval and/or anal area with sterile gauze, air-drying it, putting it into a labelled sterile container and handing it directly to local police for forensic testing before the victim's transfer for forensic assessment.18 Pregnancy risk: Depending on the victim's contraceptive and menstrual history, testing urine or serum might be useful to direct therapy and follow-up. Sexually transmissible infections: Baseline testing of sexual assault victims for sexually transmissible infections (STIs) in Australia varies with local clinical practice. In some Queensland sexual assault services serum is held in case STI testing is requested or required later (M Mobbs, Visiting Medical Officer, Brisbane Sexual Assault Service, personal communication). Baseline testing usually occurs in sexual assault services and communities with known high STI risk. As victims of sexual assault have higher rates of STIs compared with the general population,19 opportunistic screening is worthwhile if follow-up can be organised. Under Australian law, a rape victim's sexual history is inadmissible in court and this includes any history of STI. Thus, possible court prejudice is not a reason to withhold testing. See Box 4 for screening test recommendations. Note PAP smears are not generally included. The HIV/STI status of the perpetrator is usually unknown. In the absence of any better indicators, ethnicity or culture is sometimes used as a proxy for HIV/STI risk. The purpose of this judgement of risk is not to vilify minority groups, but to assess the victim's risk of infection on the basis of often very limited information about the perpetrator. Treatment recommendations alter for victims assaulted by anyone thought to be from a high risk group (see Box 5). The National HIV/AIDS Strategy states that community prevalence of HIV and STIs is higher in certain groups, including African and South-East Asian people, homosexual and bisexual men, and injecting drug users.21 Rates of STI are high in northern Australia, including in Indigenous communities,22,23 while HIV prevalence is higher in inner Sydney than elsewhere in Australia.24 As the risk of sexual transmission of hepatitis C virus (HCV) is low,25 tests are usually only performed in high risk situations (eg, assault with bleeding injuries, or assault by known HCV-positive assailant). Although the risk of HIV from one act of unprotected intercourse is very small, if the assault was penetrative unprotected vaginal or anal rape victims should be advised to use condoms until follow-up testing at three months. Most victims are concerned about HIV risk, even though they may not admit it.7 The vast majority will not require HIV prophylaxis, as the risk of transmission from an HIV-positive assailant is very small (see Box 6) and the chance that the perpetrator was HIV positive far smaller. Specific therapyCounsellingSexual assault is a frightening and sometimes life-threatening violent experience and counselling should be offered to all. Even if victims do not wish to attend counselling, it is important that they know where they can go for help, as memories can surface later (eg, at first childbirth) and can impair future functioning.27 Family and partners may also require counselling, or referral may be needed for domestic violence issues. Safety after rape can require moving house if the rapist lives with the victim, or knows where he or she lives. Emergency housing may be needed, as may other forms of immediate support, such as certificates for absence from work and support letters for school. Emergency contraceptionIf the assault was unprotected vaginal rape, or if there was any possibility that this occurred (eg, victim lost consciousness, was intoxicated or is unsure), then emergency contraception can be offered up to three, and possibly up to five, days after the assault.28 The progesterone-only regimen is recommended over the Yuzpe method because it is more effective with fewer side effects. Give the first dose as soon as possible, as efficacy halves with each 12-hour interval after the assault.29 Progesterone-only method: 750 μg levonorgestrel orally; repeat 12 hours later. A 750 μg tablet (Postinor-2, Schering Pty Ltd) is now available in Australia, or 25 30-μg tablets (Microval, Wyeth Australia Pty Ltd; or Microlut, Schering Pty Ltd) can be used for each dose. Yuzpe method: 100 μg oestradiol orally; repeat 12 hours later. Use two 50-μg oestrogen-containing combined oral contraceptive tablets for each dose. This regimen should only be used if the progesterone-only method is not tolerated or unavailable. Sexually transmitted infectionsFor unprotected vaginal or anal assault, victims are offered single-dose prophylaxis with azithromycin for chlamydia (see Box 5). They are also offered prophylactic hepatitis B vaccine if likely to be non-immune. Treatment varies according to community prevalence of STIs and perceived individual risk. In tropical areas of Australia, or if the perpetrator is considered at high risk of being infected, prophylaxis may also be added for gonorrhoea, occasionally syphilis, and passive vaccination with hepatitis B immune globulin30 may also be given if the recipient is not immune. For victims at high risk of having acquired HIV infection (eg, rape by someone from an area of high HIV prevalence), urgent phone consultation with an infectious diseases or sexual health physician about post-exposure prophylaxis for HIV is recommended (see Box 7). ReviewIt is notoriously difficult to get victims back for follow-up.31 The review program suggested (Box 4) is a guide only and should be tailored to suit individual patients. At the very least, an appointment is recommended at two weeks for discussing test results, further testing (eg, pregnancy), review of coping, and assessment of healing. Follow-up serological tests should be performed at three months for HIV, hepatitis B virus and syphilis. Reviews are a good opportunity to assess the need for counselling if this has not already been organised. Before the victim leaves, give written instructions for taking medications and review appointments, and include counselling service phone numbers. Victims may be intoxicated, shocked or tired and are unlikely to remember verbal medical instructions. SummaryManagement of acute adult sexual assault may appear daunting, but when viewed in its component parts is not difficult. Review by a sympathetic, non-judgemental practitioner can play an important role in helping victims regain control of their lives. Australia-wide resources Websites Comprehensive listing of services available in Australia and New Zealand, both updated 2002. Australia: http://www.acshp.org.au/sexual_health/assault.htm New Zealand: http://www.dsac.org.nz Major State and Territory resource phone numbers for sexual assault services The following lists only one major service for each Australian State or Territory, as these services will refer to other local services as appropriate. Australian Capital Territory Forensic and Medical Sexual Assault Care BH 02 6244 2184/3058 Canberra Rape Crisis Centre 02 6247 2525* Queensland Brisbane Sexual Assault Service 07 3636 5206* Toll free 1800 010 120* Government Medical Office (forensic regional services) 07 3405 5755* Tasmania Sexual Assault Support Service Hobart BH 03 6231 1811 AH 03 6231 1817* New South Wales Eastern and Central Sexual Assault Service, Sydney BH 02 9515 3680 AH 02 9515 6111* (ask for sexual assault counsellor) South Australia http://www.wch.sa.gov.au/yarrow/index.html Yarrow Place, Adelaide BH 08 8226 8777 AH 08 8226 8787* Toll free 1800 817 421 Western Australia Sexual Assault Resource Centre, Perth 08 9340 1820/1830 08 9340 1828* Toll free 1800 199 888* Northern Territory Darwin Sexual Assault Referral Centre 08 8922 7156* Victoria Victorian Institute of Forensic Medicine 03 9684 4444* * Denotes 24-hour contact number. 3: Guide for sexual assault care * Usually includes medical care; check with local service. † See resources section at end of article. ‡ Some rural/remote general practitioners perform forensic assessments after consultation with a sexual assault service. STI = sexually transmitted infection. 4: Baseline screening recommendations for sexually transmitted infections Infection Test Site (take according to history) HIV HIV antibody Blood Hepatitis B Hepatitis B surface antigen (HbsAg), core antibody (anti-HBc) and surface antibody (anti-HBs) Blood Syphilis Rapid plasma reagin (RPR) + treponema pallidum haemagglutination assay (TPHA) Blood Chlamydia Polymerase chain reaction Endocervical swab, first-void urine or high vaginal swab Gonorrhoea Polymerase chain reaction or microscopy, culture and sensitivity (M,C&S) Endocervical swab, first-void urine, rectal swab* or throat swab* Trichomonas Microscopy, culture and sensitivity (M,C&S) High vaginal swab * M,C&S only, as PCR is not validated for these sites. 5: Suggested prophylaxis for sexually transmitted infections (treatment for high risk is bolded) STI Treatment Chlamydia Azithromycin (1 g orally) Hepatitis B Hepatitis B vaccine (1 mL intramuscularly) For high risk add: Hepatitis B immune globulin (400 IU intramuscularly*) Gonorrhoea (only if high risk) Ceftriaxone (250 mg intramuscularly) OR, where local gonococcal sensitivities permit: 20 Ciprofloxacin (500 mg orally) OR Amoxycillin (3 g orally) and probenecid (1 g orally) Syphilis (if high risk) Benzathine penicillin (1.8 g intramuscularly) HIV (if high risk) Phone local infectious diseases or sexual health physician urgently Other STIs Consult local infectious diseases or sexual health physician * Available from Commonwealth Serum Laboratories. STI = Sexually transmitted infection. 6: HIV transmission risk per unprotected act of intercourse with an HIV-positive person*26 Type of intercourse Risk per 1000 acts Receptive anal 1–30 in 1000 Receptive vaginal 1–2 in 1000 Insertive vaginal 1 in 1000 Insertive anal 3–9 in 1000 * For comparison, the risk of acquiring HIV infection from using a shared HIV-contaminated needle is 667 in 1000, and from a needlestick injury to healthcare workers is about 4–8 in 1000. 7: Suggested review program 2–3 days: Assess injury healing if relevant 2 weeks: Test results, pregnancy testing, healing, coping Follow-up testing: Chlamydia, gonorrhoea, trichomonas (depending on local practice and whether previous treatment was given) 3 months: Follow-up serological tests for HIV, hepatitis B virus, syphilis 6 months: Follow-up serological test for hepatitis C virus if a test was performed initially

Jacqueline K Mein,*† MB BS, FACSHP, MAE · Cheryn M Palmer,† BMed, MMed, FACSHP · Meon Carol Shand,* MB ChB, FRNZCGP, FACSHP · David J Templeton,*† MB ChB, DipVen · Vanita Parek,* MB ChB, FACSHP, DRANZCOG, DipVenDFFP · Margaret Mobbs,*† MB ChB, DipVen, Visiting Medical Officer. · Kay Haig,* MB BS, FACSHP · Sarah E Huffam MB BS, FRACP · Lyndall Young MB BS, DFFP

The virus recognises the similarity of people on the planet. Scientists and policy makers must do the same. Helene Gayle (Director of the CDC's National Center for HIV, STD and TB Prevention) The AIDS epidemic is wreaking havoc and misery around the world and exposing the most awful inequalities and human frailties. In Australia, our population is relatively cocooned from this chaos (Box 1), although the conference heard of the established epidemic in our nearest neighbour to the north, Papua New Guinea, and the worrying emerging epidemic in Indonesia. Worldwide statistics can become numbing, causing human suffering to be ignored. Even for clinicians and researchers in the HIV/AIDS field, the magnitude of the problem is frequently too daunting to either comprehend or tackle in a useful way. However, the realities, and importantly the will, of good, hard-working people in the field were on display at the International AIDS Conference in Barcelona in July 2002. International AIDS conferences are amazing events, bringing the global issues surrounding HIV to the fore. They can be incredibly poignant, wonderfully motivating and equally frustrating all at the same time. Frequently, issues come into stark focus that challenge the status quo. Activists in the field of HIV/AIDS are not shrinking violets. Global access to anti-HIV medicationsWe must corner rich nations with the truth (Jeffrey Sachs, Economist and Advisor to the United Nations Secretary-General) The issue that galvanised many of the participants at Barcelona was the injustice of the lack of access to life-saving, but expensive, antiretroviral drugs in developing nations. In Barcelona, the momentum of providing global access to HIV/AIDS medicines gathered steam. The road to global access is likely to be long and full of pot-holes. The establishment of the Global Fund for AIDS, TB and Malaria provides a major focus for raising the estimated US$13 billion required per year to scale-up preventive approaches and to provide wide access to antiretroviral drugs in resource-poor nations. There was a real sense of holding political leaders accountable to ensure a more equitable future. In the words of Peter Piot, Executive Director of UNAIDS: Let's make the AIDS response truly political — let's bring forward the day when leaders who keep their promises on AIDS are rewarded with our trust, and those who don't, lose their jobs to those who will. Some political leaders were booed from the stage as the audience turned against their meagre or delayed responses to the epidemic. There have been successful pilot and expanding programs of antiretroviral treatment in several developing countries. There is growing unease that a poorly coordinated approach in the developing world will lead to the high levels of resistance to antiretrovirals now present in the developing world, squandering an opportunity to make a very major impact in these countries. Averting the errors made in antiretroviral therapy in the developed nations could potentially lead to more durable responses to antiretroviral therapy. These errors include serial monotherapy, sequential changes in the presence of imperfect HIV suppression, and decisions made to introduce new therapies on the basis of single equivalence studies measuring only short-term surrogate endpoints. The US-based AIDS Clinical Trial Group study, with 384 investigators, reported the first of the long-term strategy studies, in which outcome was based on time to first and second change of therapy in 980 individuals. This provides important information to guide treatment strategies across the globe. Essentially, the length of time to failure of first-line antiretroviral therapy was substantially longer with the initial combination of zidovudine, lamivudine and efavirenz, and the time to the second failure was substantially longer with either first- or second-drug regimens including zidovudine, lamivudine and efavirenz. No benefits of using four antiretrovirals over three were shown.1 For HIV-infected people with anti-retroviral resistance, the conference heard of encouraging efficacy reports of new drugs, such as tenofovir and T-20 (enfurvitide), as well as exciting preclinical information on integrase inhibitors. Unfortunately, the cost of these newer drugs will be prohibitive in developing countries. Not only are the treatment factors (regimen, the timing of commencement, affordable appropriate monitoring, support of adherence) important, but also support for training of healthcare professionals and commitment to ongoing funding for therapy is essential. The World Health Organization (WHO) report entitled Scaling up antiretroviral therapy in resource-limited settings continues to assist this process.2 Providing treatment for HIV is now thought to provide tremendous spin-offs for enhanced prevention. People with access to treatment are more likely to get tested for HIV infection and modify behaviour if found to be positive. Reductions in infectious virus load after treatment are likely to reduce transmission, although this is not yet definitely proven. Increasing use of medications is likely to drive global prices down. The problem of accurately taking all combination anti-retroviral therapy (adherence) continues to be shown to be a major factor affecting long-term success of therapy. To this end, an increasing number of studies of once-daily treatments are being reported. This offers practical options for improved adherence and intermittently delivered therapy (Box 2). No cureHIV treatments are most certainly not a cure. This was soberly brought home by a pioneering researcher in this field, Dr Robert Siliciano, from Johns Hopkins University, describing HIV as "intrinsically incurable". One problem lies with the dastardly ability of HIV to lie dormant in a population of cells called resting memory T cells. These cells are "designed to wait" for a lifetime to ward off previously encountered pathogens. It will prove very difficult to flush the virus out of these cells once it has taken hold. VaccinesThere is hope that a vaccine will eventually be developed that can prevent HIV infection around the world. Although this is one of the "star-wars", "high-tech" approaches to prevention, significant gains have been made in the last two years. There are three important considerations for an effective vaccine against HIV/AIDS — the vaccine must induce (i) T cell responses against virus-infected cells, (ii) neutralising antibodies against free virions, and (iii) mucosal immunity. Vaccines that induce high levels of T cell responses against HIV in animal model systems, although incapable of preventing infection altogether, are able to control viral replication for long periods. To prevent infection altogether, high levels of neutralising antibodies will be required. The induction of broadly reactive neutralising antibodies to HIV has proven very difficult, but there are now hints about potentially successful approaches. The virus is in the mucosal tissue during the first few days of infection. In 3–5 days the virus spreads and virus latency occurs. In 6–9 days the virus has spread systemically. An effective vaccine needs to work at the mucosal site of infection before systemic dissemination occurs. One major obstacle against engineering an effective vaccine is that HIV is capable of escaping both neutralising antibodies and cellular immune responses. Furthermore, there is no definitive HIV marker for protection. There were mixed reports on whether a vaccine could induce immunity across different subtypes of HIV-1 — cross-subtype T cell immune responses exist for T cell-inducing vaccines, but there are no vaccines offering a breadth of neutralising antibodies. The vaccine world is waiting with bated breath for the outcome, due to be released early in 2003, of the world's first efficacy trials in humans of HIV vaccines using envelope protein approaches with alum as the adjuvant. These trials have been conducted efficiently, albeit not without controversy, in 2500 subjects in Thailand and 5000 subjects in the United States and elsewhere. Controversies in these trials have included whether it was justifiable to proceed to human efficacy trials with vaccines that performed poorly in some preclinical studies; the provision of clean injecting equipment to trial participants; and the lack of provision of antiretroviral treatment to subjects who become infected during the trial. Encouraging reductions in risk behaviour have occurred during these efficacy trials; however, a sufficient number of seroconversions have occurred which, when the data are unblinded, should provide a robust analysis of efficacy. One final important point emphasised was that vaccine research should be complementary to, and not in competition with, therapeutic research. Other prevention approachesThe definition of insanity is doing the same thing over and over again and expecting a different result. Rita Brown (arguing for innovative programs to prevent the spread of HIV). In addition to enhanced standard prevention approaches of education, behavioural change, condoms (both male and female versions) and others, further exploration of biomedical approaches to prevention are being evaluated. Male circumcision appears to provide considerable protection from HIV, and observational studies and trials are now under way to evaluate this approach more rigorously in developing countries. Treatment of other sexually transmitted infections is now being evaluated (eg, control of herpes simplex with aciclovir) as a means of preventing HIV acquisition and transmission. Non-occupational postexposure prophylaxis with antiretrovirals is now common in many developed countries, although gathering data on its efficacy has been difficult. The spectre of pre-exposure prophlyaxis with antiretrovirals was also raised. Widespread use of antiretrovirals as pre-exposure prophylaxis has worrying implications for the development of antiretroviral resistance, but, if infection was completely prevented, resistance would not occur. Call for actionA recurring message at the conference was the need for decisive action now. As Helen Gayle said, quoting an African proverb: The best time to plant a tree was 20 years ago; the next best time is now. 1: Global distribution of the AIDS epidemic in 2001 Numbers of people living with HIV at the end of 2001 (and, in parentheses, those newly infected with HIV during 2001) as estimated by UNAIDS and WHO. Data available at: http://www.unaids.org/barcelona/presskit/graphics.html#global.htm (accessed October 2002, no longer available). 2: Once-daily HIV medications to overcome problems of adherence Currently available once-daily antiretroviral medications in Australia/USA Efavirenz Tenofovir Didanosine Ritonavir-boosted amprenavir Antiretroviral medications suggested for future development as once-daily medication Nevirapine Abacavir Other ritonavir-boosted protease inhibitors Atazanavir 3TC FTC T-1249 (fusion inhibitor) Stavudine XR (slow-release version of stavudine) 3: More quotable quotes from the Barcelona AIDS conference Helene Gayle (Director of the CDC's National Center for HIV, STD and TB Prevention, and of the Bill and Melinda Gates Foundation HIV/AIDS and Tuberculosis Program:When will justice come to Athens? Justice will come when those that are not injured are as indignant as those that are (quoting the Greek historian Thucydides). Suniti Solomon, Director, Centre for AIDS Research and Education, India:In Zambia, a widow must cry with only one eye (describing how women whose husbands die of AIDS must keep an eye on their assets, which are often seized by relatives of the deceased). Paul Farmer, Professor of Medical Anthropology, who has established a modern medical centre in a squatter settlement in central Haiti, and introduced antiretroviral treatment:Now my children are not ashamed to be seen with me (quoting a Haitian patient describing the reduction in stigma since starting antiretroviral treatment).

Stephen J Kent MB BS, MD, FRACP · C Jane Dale BSc, PhD · Anne M Mijch MB BS, FRACP

Commercially available nucleic acid amplification assays (eg, polymerase or ligase chain reaction) are now the "gold standard" tests for genital chlamydial infection and also have a role in screening for gonococcal infection. Single-dose oral antibiotics are available for treatment of Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis infections. Strains of N. gonorrhoeae in urban Australia are often penicillin resistant, while strains from South East Asia and those in homosexually active men may show high-level resistance to quinolones. Imiquimod, a novel immune-response modifier, is now available for effective, safe, self-administered treatment of genital warts. The Pap smear remains the cornerstone of screening for precursor lesions of cervical cancer, but human papillomavirus genotyping may have a role in clinical decision-making for women with equivocal or early precancerous lesions. Treatment of primary genital herpes changes the clinical course, and long-term suppressive therapy is effective for those with multiple recurrences.

Francis J Bowden FRACP, MD · Sepehr N Tabrizi PhD · Suzanne M Garland MD, FRCPA · Christopher K Fairley FRACP, PhD

To the Editor: Donovan and colleagues bring attention to the restrictions placed by the Health Insurance Commission via the Medicare system on clinicians investigating patients for sexually transmitted infections (STIs).1 In their study of Sydney general practitioners, they suggested that reform was required to the three-test pathology testing rule to improve gonorrhoea screening in high-risk individuals living in a region of epidemic gonorrhoea. In the Kimberley region of Western Australia, where we practise, syphilis, gonorrhoea and chlamydia continue to be endemic. Best-practice guidelines for primary healthcare providers in WA state that investigation for other possible STIs is essential to the care of patients with STIs or HIV infection.2 Health policy should be based on best-practice standards. For patients with confirmed or suspected STIs, this means that Medicare funding should meet the full costs of all tests for suspected STIs (as indicated by clinical need and best-practice guidelines) to enable and facilitate effective control of these infections at the population health level. An Australian legal precedent exists for medical practitioners regarding testing for STIs. In the New South Wales Supreme Court case of BT v Oei, it was found that a doctor has a duty of care to offer testing for other STIs to a patient with one STI or a suspected STI.3 In that case, a sexual partner of an HIV-positive patient brought successful legal action against her partner's doctor for failing to diagnose HIV infection in her partner. The doctor was found negligent in failing to offer an HIV test to a patient with ongoing symptoms who had been found to be infected with hepatitis B virus and whose only risk factor for this infection was unprotected sex. The doctor's duty of care was found to extend to the patient's sexual partner, who became infected with HIV after unprotected sex with her partner. Given that best-practice guidelines and a legal precedent exist which confirm that a medical practitioner should offer testing for other STIs to a patient with one STI or a suspected STI, what are the medicolegal implications of the Health Insurance Commission's three-test rule? Comment: The Journal sought a comment from the Commonwealth Department of Health and Ageing, but after three months had yet to receive a response.

Graeme H Johnson MB BS (Hons), BMedSci(Hons) · Donna B Mak FAFPHM, FACRRM

Public Health Gonorrhoea screening in general practice: perceived barriers and strategies to improve screening rates Basil Donovan, Vickie Knight, Anna M McNulty, Virginia Wynne-Markham and Michael R Kidd MJA 2001; 175: 412-414 Abstract - Methods - Results - Discussion - Acknowledgements - Competing interests - References - Authors' details - - More articles on Sexual health Abstract Objective: To investigate perceived barriers to gonorrhoea screening in general practice and suggest strategies to overcome them. Design: Questionnaire-based survey. Setting and participants: All 47 general practitioners (GPs) authorised to prescribe subsidised HIV drugs under the Pharmaceutical Benefits Scheme in inner, eastern and northern Sydney. Main outcome measures: Agreement on a five-point Likert scale with statements about attitudes and practices in relation to gonorrhoea screening of homosexually active men, and views on how testing rates could be increased. Results: 32 GPs responded (68%). Perceived barriers to gonorrhoea testing included structural measures imposed by the Federal Government to limit pathology testing by GPs (the Medicare "three-test rule") (17 respondents agreed or strongly agreed), pressure from the Health Insurance Commission (HIC) to minimise pathology testing (15), concerns about confidentiality of notification procedures (8), clinical time pressure (8), and concerns about recriminations against HIV patients with gonorrhoea (6). Suggested measures to increase testing were education of gay men to request testing (25), relaxation of the three-test rule (25), easier tests (23), anonymous notification procedures, review of HIC policy on screening, and training about testing (21 each). Conclusions: Sydney GPs with high HIV caseloads perceived structural barriers to gonorrhoea testing and supported a range of achievable strategies to overcome these. As the sustained epidemic of gonorrhoea in Sydney may be directly promoting HIV transmission, these strategies should be considered urgently. Sydney is currently in the fourth year of an epidemic of gonorrhoea among homosexually active men, with over 1000 cases reported annually in the inner city.1,2 This epidemic is of particular concern as gonorrhoea may be a marker of increased risk of HIV infection.3 Gonorrhoea also directly promotes HIV transmission,4 and treating gonorrhoea has been shown to reduce HIV levels in semen.5 Thus, these sustained high rates of gonococcal infection are likely to be leading to new, potentially preventable HIV infections. Factors that may be contributing to the epidemic are: increasing rates of unsafe sex among a subset of homosexually active men;6,7 gonorrhoea outbreaks among gay men in other industrialised cities7-9 that have links with Sydney;3 scaling down of the main public sexual health centre servicing the inner city;2,3 and limited gonorrhoea case-finding in the private sector.2 Most Australians diagnosed with sexually transmissible diseases (STDs) are managed in the private sector. Medicare, Australia's universal health insurance system, rebates or heavily subsidises patient services provided by the private sector. To minimise abuse of this system, Medicare imposes conditions, including: rebating only three pathology tests ordered by a general practitioner (GP) on any one patient on any one day (the "three-test rule"); discouraging "screening" (testing without symptoms) of patients through Health Insurance Commission (HIC) advisers, who monitor and counsel GPs about their use of pathology and radiology services; and not rebating STD testing of sex workers. While urethral gonorrhoea usually causes symptoms in men, prompting them to seek treatment, anorectal infections have variable, often subtle, symptoms,3,10 and pharyngeal gonorrhoea is asymptomatic.11 Consequently, detection of anorectal and pharyngeal gonorrhoea depends on screening according to sexual risk history, contact tracing, and maintaining a low threshold for testing. The relative infrequency of diagnosis of these infections in general practice2 suggests structural or cultural barriers to gonorrhoea screening of homosexually active men. Our study aimed to investigate these barriers and to seek solutions from a group of GPs with large numbers of patients at increased risk of gonorrhoea. Methods The study was conducted in October 1999. A one-page questionnaire was sent to all 47 GPs authorised to prescribe subsidised HIV drugs under the Pharmaceutical Benefits Scheme in inner, eastern and northern Sydney. This group was chosen because their practices were located at the centre of the gonorrhoea epidemic2 and were presumed to contain substantial numbers of homosexually active men, and because HIV-infected men are at increased risk of anorectal gonorrhoea.3The questionnaire comprised items enquiring about GPs' attitudes and practices in relation to screening homosexually active men for gonorrhoea, and their views on how STD testing rates could be increased. Questions were to be answered on a five-point Likert scale. All responses were kept anonymous. Most issues raised on the questionnaire were suggested at informal meetings with GPs with high HIV caseloads or during the pilot phase, when five such GPs were sent an earlier draft of the questionnaire for comment. Non-respondents were not prompted, as it was necessary to complete the study quickly, before commencement of a targeted community education program. Results Thirty-two of the 47 GPs (68%) returned the questionnaire. All disagreed that testing for gonorrhoea is "someone else's job", and 31 of the 32 disagreed with the suggestion that gonorrhoea is "trivial". Most respondents were aware that men at high risk of STDs who may have asymptomatic infections attended their practices and most felt competent to collect laboratory specimens. Other results are shown in the Box. Interestingly, no respondents said they treated gonorrhoea empirically without testing to avoid notification, and few were embarrassed about gonorrhoea testing or thought it would offend patients. Barriers to gonorrhoea testing perceived by respondents included Medicare's three-test rule (17 respondents agreed or strongly agreed), pressure from the HIC to minimise pathology testing (15), concerns about confidentiality of notification procedures (8), clinical time pressure (8), concerns about recriminations against HIV patients with gonorrhoea (6), and a need for the patient to raise the issue of testing (5). One respondent reported having been directly advised against STD screening by an HIC adviser, who allegedly stated that such screening was the role of public clinics. Respondents supported the following approaches to controlling gonorrhoea among homosexually active men: education to encourage gay men to ask for testing (25), relaxation of the three-test rule (25), easier gonorrhoea tests (23), anonymous STD notification procedures, review of the HIC policy on STD screening, and training about testing (21 each). Discussion The three-test pathology testing rule was the most common factor that respondents indicated was inhibiting their gonorrhoea screening: 25 of 32 respondents felt that reform was needed. A standard HIV monitoring visit includes determination of T-cell subsets, viral load and haematology and biochemistry profiles,12 which automatically exhausts any Medicare rebate for pathology providers. The cost of investigating any concurrent medical conditions, such as hepatitis C or HIV-related symptoms, must then be absorbed by the pathology service. Adding screening tests for bacterial STD (gonorrhoea, chlamydia and syphilis), particularly if required for several patients a day, inevitably strains the relationship between the ordering doctor and the pathology service. When preliminary results of this survey were presented to a general meeting of the Sydney HIV GP Study Group several GPs commented that they were distorting their clinical practice — and thus delaying necessary STD screening — to minimise the effect of the three-test rule. Clearly, policies intended to curb Medicare spending on pathology testing in general may have negative implications for STD control. The simplest solution might be to exempt testing for STDs from the three-test rule. As a precedent, an exemption has been justified for cervical cytology tests to promote screening. Clinical time pressure limiting gonorrhoea testing was an issue for a quarter of respondents. Possible solutions include moderating STD screening intervals according to level of risk, and developing screening guidelines according to results of recent research into risk factors.3 Respondents strongly supported development of easier tests for gonorrhoea. Swabbing the throat, urethra and anorectum for gonorrhoea generates three specimens. Testing the anorectum and urine for chlamydia — another emerging problem among homosexually active men8,13,14 — generates two more specimens. The reliability of gonorrhoea tests collected in general practice is unknown. There is considerable scope for research into streamlining and evaluating STD testing in general practice. Few respondents were concerned about disease notification procedures and possible repercussions for their HIV patients. However, notification might be a disincentive for some patients or their doctors, and anonymous STD notification procedures were supported by most respondents. Contact tracing was not seen as a major issue, perhaps because the identity of the source is very often not known to gay men with gonorrhoea. Nevertheless, general practice is not well structured for contact tracing, and support services could be enhanced. Acknowledgements This study was funded by the New South Wales Health Department, but the opinions expressed are not necessarily those of the Department. We thank Levinia Crooks (Australasian Society for HIV Medicine) for providing a list of authorised HIV drug prescribers, Paul Sweeney (Sydney Sexual Health Centre) for assistance with data handling, and the Sydney HIV GP Study Group for its involvement. Competing interests None declared. References New South Wales Health Department. Year in review: communicable disease surveillance, 1999. NSW Public Health Bull 2000; 11: 161-168. Donovan B, Bodsworth NJ, McNulty A, et al. Increasing gonorrhoea reports — not only in London [letter]. Lancet 2000; 355: 1908. Donovan B, Bodsworth NJ, Rohrsheim R, et al. Characteristics of homosexually active men with gonorrhoea during an epidemic. Int J STD AIDS 2001; 12: 437-443. Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect 1999; 73: 3-17. Cohen MS, Hoffman IF, Royce RA, et al. Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. Lancet 1997; 349: 1868-1873. Van de Ven P, Prestage G, French J, et al. Increase in unprotected anal intercourse with casual partners among gay men in 1996-8. Aust N Z J Public Health 1998; 22: 814-818. Page-Shafer KA, McFarland W, Kohn R, et al. Increases in unsafe sex and rectal gonorrhoea among men who have sex with men — San Francisco, California, 1994-1997. MMWR Morb Mortal Wkly Rep 1999; 48: 45-48. Handsfield HH, Whittington WLH, Desmon S, et al. Resurgent bacterial sexually transmitted diseases among men who have sex with men — King County, Washington, 1997-1999. MMWR Morb Mortal Wkly Rep 1999; 48: 773-777. Hughes G, Simms I, Rogers PA, et al. New cases seen at genitourinary medicine clinics: England 1997. Comm Dis Rep 1998; 8: S1-S11. McNulty A. Anorectal gonorrhoea revisited. Venereology 1993; 4: 109-111. Weisner PJ, Tronca E, Bonin P, et al. Clinical spectrum of pharyngeal gonococcal infection. N Engl J Med 1973; 288: 181-185. Clinical Trials and Treatments Advisory Committee (CTTAC). Model of Care for HIV Infection in Adults. Canberra: Australian National Council on AIDS and Related Diseases, 1998. Debattista J, Dwyer J, Orth D, et al. Community screening for Neisseria gonorrhoeae and Chlamydia trachomatis among patrons of sex-on-premises venues: two years later. Venereology 2000; 13: 105-109. Bloch M, Delpech V, Austin D, et al. Screening for gonorrhoea and chlamydia in gay men in an inner city primary care practice. Presented at the Australasian Sexual Health Conference Jun 2000; Darwin, NT. (Received 2 May, accepted 26 Jul 2001) Authors' details Sydney Sexual Health Centre, Sydney Hospital, Sydney, NSW. Basil Donovan, MD, FACSHP, Director, and Clinical Professor, Department of Public Health and Community Medicine, University of Sydney, NSW; Vickie Knight, RN, MHScEd, Clinical Nurse Consultant; Anna M McNulty, MM, FACSHP, Clinical Senior Manager, and Nurse Consultant, School of Community Medicine, University of New South Wales, Sydney, NSW; Virginia Wynne-Markham, Administrative Officer. Department of General Practice, University of Sydney, Sydney, NSW. Michael R Kidd, MD, FRACGP, Professor, and Head. Reprints will not be available from the authors. Correspondence: Professor B Donovan, Sydney Sexual Health Centre, Sydney Hospital, GPO Box 1614, Sydney, NSW 2001. donovanbATsesahs.nsw.gov.au Make a comment Responses of 32 general practitioners with high HIV caseloads to a questionnaire about gonorrhoea screening (in order of frequency of responses) Questionnaire item Strongly agree/ agree No opinion Strongly disagree/ disagree (Please tick the box you feel is most appropriate) Please comment on the following potential influences on your screening of homosexually active men for gonorrhoea The 3-test pathology testing rule impedes my testing for gonorrhoea and other STDs 17 1 14 I feel pressure from the Health Insurance Commission about my pathology ordering practices 15 3 14 It is necessary to swab the throat, urethra and anus of every gay man who had sex >1 partner every 3 months* 9 5 16 I have concerns about the confidentiality of the notification procedure for gonorrhoea 8 5 19 Clinical time pressures prevent me from testing for gonorrhoea 8 1 23 I'm worried about recriminations against my HIV patients with gonorrhoea† 6 3 22 I rarely think of testing my patients for gonorrhoea 6 2 24 There are too many specimens to juggle 6 1 25 The patient needs to request gonorrhoea/STD testing 5 2 25 It would offend my patients if I suggested that they need testing† 3 2 26 I am too embarrassed to do anal swabs 1 2 29 I would usually know if my patients had gonorrhoea anyway 1 1 30 I treat gonorrhoea empirically without taking a swab to avoid confidentiality/notification issues 0 1 31 Which of the following do you believe would increase testing for gonorrhoea and other STDs Gay men need to be educated to ask for regular STD testing 25 4 3 Relaxing of the 3-test rule (eg, excluding STD and HIV tests from formula)* 25 2 5 Easier pathology tests† 23 1 7 Anonymous STD notification procedure† 21 7 3 Review of Health Insurance Commission policy on frequency of STD pathology tests 21 8 3 Training or an update on gonorrhoea and STD testing† 21 4 6 STD=sexually transmissible disease. *Two general practitioners did not respond to this question. †One general practitioner did not respond to this question. 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Basil Donovan · Vickie Knight · Anna M McNulty · Virginia Wynne-Markham · Michael R Kidd

Conference Report XIII International AIDS Conference, Durban, 9-14 July, 2000 Nelson Mandela argues for urgent action against HIV in Africa John B Ziegler and Rosemary A Ffrench Let us not equivocate: a tragedy of unprecedented proportions is unfolding in Africa. AIDS today in Africa is claiming more lives than the sum total of all wars, famines and floods, and the ravages of such deadly diseases as malaria . . . Economic growth is being undermined and scarce development resources have to be diverted to deal with the consequences of the pandemic . . . Decades have been chopped from life expectancy and young child mortality is expected to more than double in the most severely affected countries of Africa. AIDS is clearly a disaster, effectively wiping out the development gains of the past decades and sabotaging the future. Earlier this week we were shocked to learn that within South Africa one in two, that is half, of our young people will die of AIDS. The most frightening thing is that all of these infections, which statistics tell us about, and the attendant human suffering, could have been, can be, prevented. Something must be done as a matter of the greatest urgency. And with nearly two decades of dealing with the epidemic, we now do have some experience of what works.-- Nelson Mandela1 MJA 2000; 173: 572-574 Prevention - Mother-to-child transmission - Vaccines - Treatment strategies - Hope - References - Authors' details Box 1: HIV in African countries, 1999 Box 2: Trends in mortality among children under five Nelson Mandela's closing address to the conference1 was a welcome contrast to the opening address by Thabo Mbeki, President of South Africa, who disappointed delegates by failing to resolve their concerns about his view that HIV does not cause AIDS. In his plenary address, David Ho (Director, Aaron Diamond AIDS Research Center, New York) noted that Mbeki would be judged harshly by history. Judge Ed Cameron, a gay white South African living with HIV, in a moving address, pointed out that his government had consistently mismanaged the epidemic, and that he was only alive because his income allowed him to purchase antiviral drugs not available to most South Africans with AIDS. Prevention Box 3: Probability of a Zimbabwean boy aged 15 dying before age 50 Box 4: Projected population structure, Botswana 2020 While news of the explosive spread of HIV in the Republic of South Africa highlighted the urgency of effective preventive strategies, there was relatively good news from some countries where decisive action by pragmatic governments was paying off: the HIV infection rate has stabilised at a relatively low level in Senegal; Uganda has brought its estimated prevalence rate down to about 8% from a peak of close to 14% in the early 1990s; Thailand's "100% condom use" campaign among female sex workers has contributed to falling prevalence in military recruits and antenatal clinic patients.2 In the opening plenary session, Professor Roy Anderson (Director, Centre for the Epidemiology of Infectious Disease, Oxford) explained that interventions to interrupt the spread of HIV in populations would have relatively little impact once prevalence was high. Targeting individuals engaging in high risk behaviours was only effective early in an epidemic; unfortunately, few governments have been prepared to invest resources in the early stages, when such efforts are most cost-effective. There was hope that relatively inexpensive strategies to prevent heterosexual transmission of HIV might emerge from the conference. Unfortunately, the results of a study of a vaginal microbicide containing nonoxynol-9 among sex workers in Côte d'Ivoire showed a higher infection rate in the experimental arm. This suggests that the microbicide's detergent action caused ulceration that enhanced HIV transmissibility. Mother-to-child transmission Amid the gloom of the inexorable spread of HIV in Africa and emerging epidemics in Eastern Europe, delegates were virtually unanimous that there should be no delay in implementing cost-effective measures to prevent mother-to-child transmission of HIV, especially with some drug companies offering to provide free drugs in less developed countries. Data from a prospective observational study in the USA showed that, with optimal maternal combination antiretroviral treatment, the risk of mother-to-child transmission falls to as low as 1%. In breast feeding populations treated with only one drug the gains were less dramatic, but nevertheless very impressive, with the potential to prevent the infection of 25 000 infants a year in South Africa alone. Data presented at the conference reinforced concern that the benefit of perinatal antiviral therapy would be lost when mother-to-child transmission occurred during subsequent breast feeding. However, analysis of the HIVNET 012 trial (mother and infant each received a single dose of nevirapine in labour and by Day 3, respectively) at 18 months showed that an absolute 8% reduction persisted despite prolonged breast-feeding.3 These interventions prevent only about a third of mother-to-child transmission, but they point to cost-effective strategies relevant in resource-poor settings. Implementation will be challenging; it was clear that many women attending African antenatal clinics do not accept HIV screening, do not return for results or do not accept antiretrovirals if HIV positive; attrition rates of 80% were reported. The role of breast feeding in perinatal transmission of HIV was firmly established by a randomised, controlled trial in Nairobi, Kenya.4 While observational data suggested that exclusive breast feeding may be safer than mixed feeding, bottle feeding provides the best protection against HIV infection. The Nairobi investigators reported that the mode of feeding did not affect survival to 24 months, either in the infected or uninfected infants. Surprisingly, breast feeding was associated with three times as much maternal mortality at two years as formula feeding. Vaccines New candidate HIV vaccines presented at the conference provided some hope for the future control of the pandemic. After the disappointing immunogenicity of the recombinant protein vaccines, which were designed to elicit antibody responses, it was thought that strategies for eliciting cellular immunity, particularly cytotoxic T lymphocyte (CTL) activity, may be more successful. The trials of vCP205 (a canarypox virus expressing HIV genes), both alone or with a recombinant protein boost, showed very few vaccine recipients with detectable CTL activity, and these few responses were not sustained. However, it was shown that responses were detected more frequently when vaccine recipients received higher doses of vCP205, so more antigen expresssion may be necessary to achieve the desired levels of immunity. Results of a Phase II trial of the whole, killed HIV vaccine, Remune, in HIV-positive individuals in Thailand were presented. The subjects who received the therapeutic vaccine had a small but significant increase in the CD4+ cell count (P = 0.05) of about 46 cells/µL, with increased antibody levels but no change in viral load. Probably the most controversial decision relating to HIV vaccines in the past few years was to take the AIDSVAX recombinant envelope protein into Phase III clinical trials (in Phase I/II trials the vaccine did not induce antibodies that would neutralise circulating strains of HIV). It was reported in Durban that enrolment in the Phase III trials had been completed in Thailand (n = 2100) and the USA (n = 5400). Efficacy data will not be available until early 2003. There are many new vaccine concepts currently undergoing preclinical testing and some impressive data were presented on experiments in mice and macaques. Stephen Kent (Principal Research Fellow, HIV Vaccines Laboratory, University of Melbourne) presented further evidence that a prime-boost vaccine strategy using DNA vectors, followed by fowlpox virus recombinant for gag and pol simian immunodeficiency virus genes, produced very high levels of cellular immunity in macaques, and that these responses could be increased by the co-expression of the cytokine gene IFN-g. This candidate vaccination strategy, for which the University of New South Wales was recently awarded $27 million by the US National Institutes of Health (NIH), will be tested in Phase I/II human clinical trials in Australia within two years. Another vaccine that has generated considerable interest was presented by Dr Robert Johnson (Director, Alphavax, Professor of Virology, University of North Carolina). The vector for the vaccine, a Venezuelan equine encephalitis replicon, was shown to target dendritic cells, one of the most powerful inducers of cellular immune responses. Testing of this vaccine will begin in South Africa early next year. Dr B. Ensoli (Virologist, Instituto Superiore di Sanità, Rome) also presented some convincing data on preclinical macaque studies of a vaccine targeting immune responses to the tat gene of HIV. She found that five of seven macaques were protected from infection with pathogenic simian/human immunodeficiency virus challenge, and that these monkeys had developed good cellular immune responses to tat protein. Clinical trials are due to begin with this vaccine in Italy and Africa. Thus, although HIV vaccines tested to date have produced somewhat disappointing results, there was optimism at Durban that the next generation of vaccines are promising. Treatment strategies Clinicians and patients have recently become excited by the concept of structured treatment interruptions, which have been suggested to enhance immune responses to HIV while providing relief from the cost, inconvenience and toxicity of complex antiretroviral regimens. Dr Tony Fauci (Director, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland) presented a pilot study of five patients selected because they had achieved undetectable viral levels with potent therapy. They then interrupted therapy for one week in two. During seven such interruption cycles the patients' viral levels remained undetectable and their immune function was preserved. However, because the cohort was small, the subjects highly selected (with extremely well controlled viral replication) and the period of observation was too short, the results did not provide reassurance that such a strategy would not be associated with the risk of induction of drug-resistant variants. It is thus much too early to recommend this strategy in clinical practice. Hope Overall, the conference was hugely successful. Despite talk of boycotts because of Mbeki's views, the conference was well attended. The colourful national costumes of delegates, signage, art and craft displays and street theatre all provided a celebratory atmosphere. There was a mood of optimism that the problems of access to treatments in resource-poor countries were at last beginning to be addressed. Simple, cost-effective, population-based prevention strategies are working in those countries which have implemented them. The hope is that an affordable preventive vaccine that is active against strains of HIV in areas of high prevalence is not too far off. References Closing address by former President Nelson Mandela at the 13th International AIDS Conference, 14 July 2000, Durban. <http://www.aids2000.com/> Accessed 1 November 2000. UNAIDS. Report on the global HIV/AIDS epidemic, June 2000.<http://www.unaids.org/epidemic_update/report/index.html> Accessed 1 November 2000. Guay LA, Musoke P, Fleming T, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. Lancet 1999; 354: 795-802. Nduati R, John G, Mbori-Ngacha D, et al. Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized clinical trial. JAMA 2000; 283: 1167-1174. Authors' details Department of Immunology, Sydney Children's Hospital, Sydney, NSW. John B Ziegler, MD, FRACP, Associate Professor. Rosemary A Ffrench, PhD, Senior Scientist, Research Laboratory. Reprints will not be available from the authors. Correspondence: Associate Professor J B Ziegler, Department of Immunology, Sydney Children's Hospital, High Street, Randwick, NSW 2031. j.zieglerATunsw.edu.au 1: Seroprevalence of HIV in African countries in 1999 Over the last decade HIV has spread dramatically in sub-Saharan Africa, the fastest increases in prevalence occurring in Eastern and Southern Africa. (Reproduced by kind permission of the Joint United Nations Progamme on HIV [UNAIDS].) Back to text 2: Trends in mortality among children under five years old, with reference to adult HIV prevalence rate at the end of 1999 During the 1980s there were impressive improvements in child mortality attributable at least in part to improved immunisation rates, better management of diarrhoeal and respiratory disease and economic development. However, those gains are being lost and the increased child mortality rates are attributable to increasing incidence of perinatally acquired HIV. (Source: Demographic and Health Surveys, Macro Intenational, USA.) Back to text 3: Probability of a Zimbabwean boy aged 15 years dying before age 50 Trends are shown according to data from various national surveys. In high prevalance countries, a teenager has a greater than 50% chance of dying of AIDS before age 50. (Source: Feeney G, unpublished data, 1999.) Back to text 4: Projected population structure with and without the AIDS epidemic, Botswana 2020 The population chimney graph shows the dramatic impact that AIDS is predicted to have on the structure of the population of Botswana, where over a third of the 775 000 adults are now infected with HIV. The red pyramid shows the population structure as it would be in the absence of an AIDS epidemic. More children would be born (because more mothers would survive and remain fertile throughout their reproductive years) and fewer would have died because they acquired the virus from their mothers. Far fewer young adults would die before old age. The yellow areas show that the burden of AIDS will be greatest in children and in the most economically productive years of adult life. The implications of this change in population structure are shocking. The United States Census Bureau projects that in 20 years' time there will be more adults in their 60s and 70s in Botswana than in their 40s and 50s. This is based on the assumption that patterns of new infection will not change greatly over the next decade; however, as changes in future infection rates will principally affect men and women under 40 in 2020, the demographic chimney pattern for older adults is hardly affected by this assumption. The "missing adults" -- men and women who should have reached their 40s and 50s in 2020 -- are now in their 20s and 30s, although some have already died. Many more are already infected with HIV and will die before they reach their 50s.2 (Source: US Census Bureau, World Population Profile 2000.) Back to text

John B Ziegler · Rosemary A Ffrench

Abstract Cardiovascular risk factors are commonly associated with erectile dysfunction and should be identified and treated. Patients with cardiovascular diseases should be assessed and counselled regarding their fitness for sexual activity. The danger of concurrent use of sildenafil and nitrates under any circumstances, regardless of age and sex, must be highlighted at all levels of the community. Sildenafil is absolutely contraindicated in patients receiving treatment with long-acting nitrates for ischaemic heart disease. Patients who need sublingual short-acting nitrates infrequently should not be precluded from taking sildenafil, provided they are aware that sildenafil is not to be taken within 24 h of taking the nitrate. There has been concern about the use of sildenafil (Viagra; Pfizer) for the treatment of erectile dysfunction (ED), particularly with regard to its possible role in the reported deaths and other serious cardiovascular events. Although sildenafil attracted considerable free media publicity in its debut in Australia and ranks as the most publicised new product this decade,1,2 consumer interest has been subdued and partly overshadowed by reports of 130 deaths involving sildenafil users in the United States between late March and mid-November 1998.3 It is therefore important that the association between sildenafil and these deaths be examined critically, so that the nature and the degree of risk may be identified and proper guidelines may evolve for the use of sildenafil. Cardiovascular disease and erectile dysfunction Cardiovascular disease and ED are known to be associated. In the Massachusetts Male Ageing Study,4 moderate or complete ED was 31% more prevalent among people with heart disease than in an age-matched cohort without heart disease. In a study in Perth, WA, the prevalence of complete ED among patients with hypertension, ischaemic heart disease and peripheral vascular disease was 26%, 38% and 57%, respectively, compared with 18.6% for the whole study.5 Reported ED in patients hospitalised for myocardial infarct or coronary artery surgery is of the order of 57%-64%.6,7 Conversely, in patients with severe ED, there is a 16% risk of severe, clinically occult ischaemic heart disease.8 Indeed, a statistically significant correlation has been shown between ED and the number of occluded coronary vessels.9 A significant number of patients requesting treatment for ED will have known or undiagnosed ischaemic heart disease, leading to considerable potential for adverse cardiovascular events. Moreover, many medications used for the treatment of cardiovascular disease may aggravate ED or complicate its treatment.10 Sildenafil and erectile dysfunction Sexual stimulation leads to the release of nitric oxide in the corpus cavernosum and results in an increase of cyclic guanosine monophosphate (cGMP), which produces smooth muscle relaxation and increased blood flow. Sildenafil is a selective inhibitor of cGMP-specific type 5 phosphodiesterase (PDE), the enzyme responsible for the degradation of cGMP in the corpus cavernosum. Thus, it enhances the effects of cGMP and permits an erectile response to be achieved or sustained (Box 1). The relevant pharmacodynamic and pharmacokinetic characteristics of sildenafil are summarised in Box 2.11-13 The efficacy of sildenafil in the treatment of ED has been demonstrated in 21 randomised, double-blind, placebo-controlled trials involving more than 3000 patients aged 19-87 years with ED of various aetiology.11 Sildenafil has been studied in men with ischaemic heart disease and with a wide range of other risk factors.14 A low incidence of serious or clinically significant adverse events, including cardiovascular events, was reported, comparable to that in patients with no known history of cardiovascular disorders. In Phase II-III studies involving 349 placebo patient-years and 693 sildenafil patient-years in randomised studies and 4220 patient-years in open-label studies, the incidence of myocardial infarction was lower in the sildenafil group than in the placebo group, although the difference was not statistically significant. The incidence of adverse events attributable to lowering of blood pressure in patients taking sildenafil was also low and no higher than in those receiving placebo. It was similar in patients taking concomitant antihypertensives and in those not taking these medications.14 There were reports of 26 deaths in about 5000 sildenafil patient-years, including 14 people with myocardial infarction and sudden death. None of the deaths was considered to be treatment related.14 Sildenafil and adverse cardiovascular events The unprecedented hype generated by the launch of sildenafil in the United States was dampened by reports of cardiovascular events, including deaths, allegedly associated with its use. A summary of reports of death among sildenafil users was posted by the Food and Drug Administration (FDA), with the pertinent remark that, in interpreting these reports, consideration should be given to the limitations of spontaneous reporting, such as under-reporting, duplication, marketing and medicolegal factors, incomplete or inaccurate clinical information, and the assumption of a cause-effect relationship.3 An overview of the FDA's updated summary of 130 reports of death between late March and mid-November 1998 is shown in Box 3. Deaths have also been reported in the Netherlands15 and Australia.16 Did sildenafil cause or contribute to the reported deaths? Sexual activity remains a potential trigger for myocardial infarction and sudden death may result from ischaemia or arrhythmia, although the relative and absolute risks are apparently low (Box 4). In the US general population with an age distribution similar to that of sildenafil users, there are about 400 deaths per million per week, and about 150 of these have a cardiovascular cause.29 In Australia, there are about 250 myocardial infarctions (50 fatal) per week affecting men aged 35 to 69 years.30,31 More than 70% of the deceased subjects in the FDA summary had overt or occult cardiovascular disease. Considering the high prevalence of risk factors for sudden cardiac death in users of sildenafil, the reported 130 deaths need to be viewed in the context of patient exposure to about 50 million sildenafil tablets, or more than 6 million prescriptions, during the same period. Pharmacologically, the action of sildenafil as a type 5 PDE inhibitor is highly specific. Potential for disaster seems to lie in the concurrent use of sildenafil and organic nitrates, as sildenafil potentiates the effect of nitrates and may lead to life-threatening hypotension (Box 1). Among the deaths reported in the FDA summary, there were 16-19 sildenafil users who had allegedly used or received glyceryl trinitrate or a nitrate-containing medication. In this subset of individuals, the concurrent use of nitrates would provide the possible causal link between sildenafil and death. Therefore, it is not unlikely that sexual activity in a vulnerable person and adverse drug interaction caused or contributed to the reported deaths. Recommendations Box 5 shows the recommended strategy for treating ED. To minimise adverse consequences, it is important that a patient's fitness for sexual and physical activity be assessed when treatment of ED is considered, and that the patient be appropriately counselled if sexual activity is inadvisable. In general, sexual intercourse should be safe if a patient can perform an activity equal to 5-6 metabolic equivalents (METS), such as climbing 20 stairs in 10-15 seconds without distress.32 Postinfarction patients who reach 5-6 METS on stress testing without ischaemia or arrhythmia can resume their normal sexual activity without risk.33 In one study, patients with a negative exercise test result did not demonstrate ischaemia on Holter monitoring during sexual intercourse.26 The frequent use of short-acting nitrates and ongoing therapy with long-acting nitrates are absolute contraindications to the use of sildenafil. The only option for patients in this situation is to avoid the use of sildenafil. A policy of refraining totally from the use of sildenafil in all patients receiving nitrates in whatever form and regardless of frequency would, of course, quarantine patients from the risk of drug interaction. Nevertheless, patients who have only an infrequent need for short-acting nitrates, such as sublingual glyceryl trinitrate, should not be precluded from the use of sildenafil. However, doctors need to ensure that patients fully understand the implications of the potential interaction of these therapies. Patients whose only exposure to nitrate therapy is infrequent use of sublingual glyceryl trinitrate tablets or spray should be advised that at least 24 hours from the last use of the short-acting nitrates should be allowed to elapse before the use of sildenafil. It is not definitely known when nitrates can be safely administered after a dose of sildenafil. Certainly, patients should be cautioned against the use of any form of nitrates for at least 24 hours after sildenafil. In elderly patients, and in those with hepatic and renal impairment or receiving medications which may inhibit the cytochrome P450 3A4 isoenzyme (eg, erythromycin, fluconazole, fluoxetine, cimetidine), consideration must be given to decreased sildenafil clearance. If a patient should develop angina within 24 hours of taking sildenafil, nitrates should be totally avoided. Doctors should ensure that their patients follow this advice carefully. If necessary, an increase in the dose of alternative anti-anginal agents should be considered. If a patient requires hospital admission, non-nitrate anti-anginal preparations such as ß-blockers or calcium-channel blockers can be used with due regard to the risk of hypotension. If complications should develop from the inadvertent concurrent use of a nitrate, the recommendations of the American College of Cardiology and the American Heart Association34 should be followed. These include resuscitative measures such as fluid infusion and judicious use of intravenous vasopressors to maintain blood pressure, as well as appropriate non-nitrate anti-anginal agents. If adherence to such guidelines is difficult, the alternative is to avoid sildenafil in favour of other therapeutic options for ED. Clinical judgement and discretion must prevail over generalisation, bearing in mind the risk and benefit and the priority of the therapeutic interventions involved. There are no established data on the safety and efficacy of sildenafil in patients with myocardial infarction or life-threatening arrhythmia within the preceding six months; patients with systolic blood pressure < 90 mmHg; or patients with cardiac failure or coronary artery disease causing unstable angina. Caution must be exercised in prescribing sildenafil for these patients and for patients receiving complicated multidrug antihypertensive therapy.34 Where appropriate, monitoring of blood pressure at the initiation of sildenafil therapy would identify patients with a hypotensive response to sildenafil. An appropriate educational program will reduce the risk of drug interaction by alerting pharmacists and doctors to the potential danger. Pharmaceutical companies marketing nitrate-containing medications should specify sildenafil as a contraindication in their product information. Paramedics, nursing staff, patients and the community at large should be instructed on the danger of the concurrent use of sildenafil and nitrates, and of the undesirable practice of sharing medication with relatives and friends (Box 6). It is important that a warning be given to every patient, regardless of sex or age. Women have been known to use sildenafil to heighten sexual arousal and young people may use amyl nitrite inhalation for recreational pursuit. Cardiovascular diseases affect an estimated 2.3 million Australians.35 The risk of angina increases with age, affecting 12.4% of men and 11.7% of women aged 65-69 years.36 These proportions are likely to be greater among patients with ED. A request for treatment of ED provides a window of opportunity to assess the patient for cardiovascular and other risk factors, including diabetes and abnormal lipid profile. Cardiovascular risk factors, if identified, should be vigorously treated according to established guidelines.37,38 The sildenafil controversy continues.39 It has been reported that the FDA continues to believe that sildenafil remains safe.39 However, continuing postmarketing surveillance is essential for sildenafil, as for any recently marketed drug. Disclosure B G A Stuckey has served as a principal investigator in clinical studies of sildenafil. K K Chew and B G A Stuckey have received sponsorship to attend conferences from Pfizer Aust Pty Ltd. P L Thompson serves on the international steering committee of a Pfizer-sponsored clinical trial of lipid lowering in the elderly. K K Chew, B G A Stuckey and P L Thompson have been invited to present papers at Pfizer-sponsored meetings. References Kiely M. Viagra saturates media. Marketing Globe. Marketing 1998; Dec: 58. Jones A. When the thrill has gone. Business Rev Weekly 1999; June 25: 90-95. US Department of Health, Food and Drug Administration. Postmarketing safety of sildenafil citrate (Viagra) and summary of reports of death in Viagra users received from marketing (late March through mid-November 1988). 24 November 1988. Feldman HA, McKinlay JB, Goldstein I, Longcope C. Erectile dysfunction, cardiovascular disease and cardiovascular risk factors: prospective results in a large random sample of Massachusetts men. J Urol 1998; 159 Suppl 5: 91 abstract 347. Chew KK, Earle CM, Stuckey BGA, et al. Erectile dysfunction in general medical practice: prevalence and clinical correlates. Int J Impot Res 2000; 12: 1-5. Wabrek AJ, Burchell RC. Male sexual dysfunction associated with coronary heart disease. Arch Sex Behav 1980; 9: 69-75. Gundle MJ, Reeves BR, Tate S, et al. Psychosocial outcome after aortocoronary artery surgery. Am J Psychiatry 1980; 137: 1591-1594. Anderson M, Nicholson B, Louie E, Mulhall JP. An analysis of vasculogenic erectile dysfunction as a potential predictor of occult cardiac disease. J Urol 1998; 159 Suppl 5: 30 abstract 118. Greenstein A, Chen J, Miller H, et al. Does severity of ischaemic coronary disease correlate with erectile function? Int J Impot Res 1997; 9: 123-126. Slag MF, Morley JE, Elson MK, et al. Impotence in medical clinic outpatients. JAMA 1983; 249: 1736-1740. Morales A, Gingell G, Collins M, et al. Clinical safety of sildenafil citrate (Viagra) in the treatment of erectile dysfunction. Int J Impot Res 1998; 10: 69-74. Viagra -- approved product information. Pfizer, 1998. Boolell M, Allen MJ, Ballard SA, et al. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 1996; 8: 47-52. Zusman RM, editor. Cardiovascular data on sildenafil citrate. Am J Cardiol 1999; 83(5A). Feenstra J, van Drie-Pierik RJHM, Lacle CF, Stricker BHC. Acute myocardial infarction associated with sildenafil. Lancet 1998; 352: 957-958. Viagra is here! Australian Adverse Drug Reactions Bulletin 1998; 17(4). Hellerstein HK, Friedman EH. Sexual activity and the postcoronary patient. Arch Intern Med 1970; 125: 987-999. Bohlen Y, Held JP, Sanderson MO, Paterson RP. Heart rate, rate-pressure product, and oxygen uptake during four sexual activities. Arch Intern Med 1974; 144: 1745-1748. Willich SN, Klatt S, Arntz HR. Circadian variation and triggers of acute coronary syndromes. Eur Heart J 1998; 19 Suppl C: C12-23. Nalbangtil I, Yigitbasi O, Kiliccioglu B. Sudden death in sexual activity. Am Heart J 1976; 91: 405-406. Ueno M. The so-called coital death. Jpn J Legal Med 1963; 17: 330-340. Renshaw DC, Karstaedt A. Is there (sex) life after coronary bypass? Comp Ther 1988; 14: 61-66. Lecomte D, Fornes P, Nicolas G. Stressful events as a trigger of sudden death: a study of 43 medico-legal autopsy cases. Forensic Sci Int 1996; 79: 1-10. Muller JE, Mittleman MA, Maclure M, et al. Triggering myocardial infarction by sexual activity. JAMA 1996; 275: 1405-1409. Johnston BL, Fletcher GF. Dynamic electrocardiographic recording during sexual activity in recent post-myocardial infarction and revascularization patients. Am Heart J 1979; 98: 736-741. Drory Y, Shapira I, Fisman EZ, Pines A. Myocardial ischaemia during sexual activity in patients with coronary artery disease. Am J Cardiol 1995; 75: 835-837. Kavanagh T, Shephard RJ. Sexual activity after myocardial infarction CMAJ 1977; 116: 1250-1253. Paolillo V, Marra S, Spadaccini F, Angelino PF. Dynamic electrocardiographic recording during sexual activity in recent post-myocardial infarction and revascularization patients [letter]. Am Heart J 1980; 100: 763. Health United States. 1998. Hyattsville, Maryland: US National Center for Health Statistics, 1998. Australian Institute of Health and Welfare. Heart, stroke and vascular diseases, Australian facts. Canberra: AIHW and the Heart Foundation of Australia, 1999. (Cardiovascular Disease Series No. 10. AIHW Cat. No. CVD 7.) Australian Bureau of Statistics. Causes of death, Australia. Canberra: ABS, 1997. (Cat No. 3303.0.) Cardiac rehabilitation: sex after a heart attack. In: Zaret BL, Moser M, Cohen LS, editors. Yale University School of Medicine Heart Book. New York: Hearst Books, 1992; 351. Tardif GS. Sexual activity after a myocardial infarction. Arch Phys Med Rehabil 1989; 70: 763-766. Summary statement of the American College of Cardiology and the American Heart Association on the use of sildenafil (Viagra) in patients at clinical risk from cardiovascular effects. 10 August 1998. <http://www.americanheart.org/ Whats_News/AHA_Science_Advisories/viagra.html>. Accessed 18 February 2000. Fact sheet for prevention of myocardial infarction. National Heart Foundation of Australia. Curr Ther 1999; 39: 52. Fact sheet for angina. National Heart Foundation of Australia. Curr Ther 1999; 39: 63. Grundy SM, Balady GJ, Criqui MH, et al. Guide to primary prevention of cardiovascular diseases. A statement for healthcare professionals from the Task Force on Risk Reduction. Circulation 1997; 95: 2329-2331. Heart Foundation of Australia. Guide for the use of lipid lowering drugs in adults. Canberra: Heart Foundation of Australia, 1999. Available at <http://www. heartfoundation.com.au/include/defaultStory.asp?OwnerUID=200&Content Type=tblcategory>. Mitka M. Some men who take Viagra die -- why? [news]. JAMA 2000; 283(5). <http://jama.ama-assn.org/issues/v283n5/full/jmn0202-2.html>. Accessed 18 February 2000. (Received 8 Oct 1999, accepted 14 Feb 2000) Authors' details Keogh Institute for Medical Research, Perth, WA. K Kim Chew, FRCP(Edin), FRCP(Glas), Senior Clinical Fellow; Bronwyn G A Stuckey, MB BS, FRACP, Medical Director, and Consultant Endocrinologist, Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, WA. University of Western Australia, Perth, WA. Peter L Thompson, FRACP, FACP, Clinical Professor of Medicine, University of Western Australia, and Consultant Cardiologist, Sir Charles Gairdner Hospital, Perth, WA. Reprints will not be available from the authors. Correspondence: Dr B G A Stuckey, Keogh Institute for Medical Research, 3rd Floor A Block, Queen Elizabeth II Medical Centre, 2 Verdun Street, Nedlands, WA 6009. rmriATwt.com.au 2: Pharmacodynamic and pharmacokinetic characteristics of sildenafil11-13 Sildenafil is about 4000-fold more selective for type 5 phosphodiesterase (PDE5) than for PDE3, which is involved in cardiac contractility. In healthy volunteers, sildenafil produced a modest decrease in blood pressure (up to 8.4 mmHg systolic and 5.5 mmHg diastolic), but no consistent orthostatic effects and no clinically relevant electrocardiographic changes. In patients receiving medications containing nitrates, the hypotensive effects of sildenafil can be severe. In a US study with isosorbide mononitrate 20 mg twice daily, 50 mg sildenafil produced maximal blood pressure reductions of 40.9 mmHg systolic sitting and 51.6 mmHg systolic standing, and 25.8 mmHg diastolic sitting and 29.3 mmHg diastolic standing, about one hour after dosing and lasting up to 6 h. Similar haemodynamic interaction occurred for about two hours after a dose of 500 µg sublingual glyceryl trinitrate (maximum reductions: systolic, 36.0 mmHg sitting; diastolic, 20.5 mmHg sitting). Sildenafil has a half-life of about 4 h. After an oral dose of 100 mg, the plasma level peaks at about 440 ng/mL within 30-120 min, and drops to about 2 ng/mL at 24 h. Sildenafil is predominantly metabolised in the liver by the cytochrome P450 3A4 system, and 18% of the dose is excreted in the urine. Increased plasma levels may result from concomitant use of a cytochrome P450 3A4 inhibitor (eg, erythromycin, fluconazole, fluoxetine, cimetidine) or reduced clearance in elderly persons (>65 years) and in those with significant hepatic and renal impairment (creatine clearance <30 mL/min). 3: US Food and Drug Administration summary of reports of death in sildenafil users Number of deaths reported130Number with cause not mentioned or unknown48Number from homicide or drowning2Number from stroke3Number from cardiovascular events Definite or suspected myocardial infarction Cardiac arrest Cardiac symptoms Coronary artery disease77 41 27 6 3Use of nitrates Took or were administered a nitrate medication Found with nitrate in their possession16 3Time of death after use of sildenafil Not stated or unknown Within 4-5 hours of using sildenafil (includes 27 during or immediately after sexual intercourse) Later the same day Next day Two days later Three to seven days later61 44 6 8 5 4Cardiovascular risk factors One or more risk factors No identified risk factors, but severe coronary artery disease found at autopsy No history of cardiac disease or risk factors No risk factors and no sexual activity Not specified 90 3 12 2 23 4: Sexual activity and adverse cardiovascular events Sexual activity, like any other physical effort, increases cardiac work and myocardial oxygen demand.17 Heart rate and blood pressure rise to an energy expenditure of 2.0-5.4 metabolic equivalents.18 Sexual activity may trigger an adverse cardiovascular event.19,20 Coital death has been reported to account for 0.6% of sudden deaths,21 although it is said to be rare in a stable sexual relationship.22 In a study of 43 cases, sudden death was found to occur primarily in patients with severe heart disease, especially coronary heart disease, and in only three cases was sexual activity involved.23 In another study, 9% of patients reported having had sexual activity in the 24 hours, and 3% in the two hours, preceding myocardial infarction. The relative risk of myocardial infarction occurring in the two hours after sexual activity was estimated to be 2.5, and was not increased in patients with a history of previous angina pectoris or myocardial infarction. The absolute risk increase was low, at one chance in a million for a healthy individual.24 Electrocardiographic abnormalities during sexual activity have been reported in 12 of 24 patients with recent myocardial infarction or revascularisation.25 In another study, 31% of men with ischaemic heart disease had ischaemia on Holter monitoring during sexual intercourse, although only 7% were symptomatic.26 However, the frequency of angina pectoris and ventricular premature beats is less during sexual intercourse than during standard laboratory exercise, and sexual relations are thought to carry no special risk for the average postinfarction patient.27 Sexual activity in the early posthospital phase of myocardial infarction is not a stronger stimulus than other activities for cardiac electrical instability.28 Anxious sexual preoccupation, frustration and avoidance may actually be greater risk factors than coitus or coital alternatives.22

Peter L Thompson

Sex, Science & Society Sex, reproduction and impregnation: by 2099 let's not confuse them Since prehistoric times humans have had sex for reasons other than reproduction Robert P S Jansen MJA 1999; 171: 666-667 Introduction - Impregnation's risks and benefits - Reproduction and choice - Sex and vulnerability - References - Authors' details - - More articles on Sexual health Introduction Impregnation -- the entry of sperm into the female body -- is a powerful biological, emotional and social event. Sex is also each of these things. So too is reproduction, or having children. It is important not to confuse the three. Impregnation's risks and benefits The human body is no zoological fortress, as the medical fields of virology, bacteriology and parasitology make clear.1,2 Spermatozoa introduced to the reproductive mucosa or elsewhere will sooner or later be phagocytosed by macrophages. Nonetheless, sperm are intrepid: sperm heads can persist in macrophages for seven days or more and, in mice, tritiated-thymidine-labelled DNA from sperm heads in the reproductive tract has been found not just in the uterus, but in the ovaries, the lymph nodes, the spleen, and even the heart.2,3 Through their display of polycationic binding sites, spermatozoa can act as vectors for foreign DNA.4 HIV is concentrated in seminal plasma.1The chasm that has opened between sex and reproduction needs a paradigm more understanding than abstinence or furtiveness. Given these risks, why accept impregnation? The one rational reason is for reproduction. Otherwise impregnation appears to be a non-essential side-effect of sex. However, whether fertilisation takes place internally or in vitro, there may be biological benefit to non-conceptional exposure of a woman's immune system to her mate's antigens before reproduction. An increased likelihood of subsequent embryonic survival5,6 and protection against eclampsia7,8 have both been suggested as possible biological benefits of impregnation for a time before conception occurs. Reproduction and choice Unless impregnation has been forced,9 a woman nowadays can more or less choose to whose sperm her eggs will be exposed. Ordinarily, she can choose who her mate will be, or she might choose a sperm donor from a commercial sperm bank, such as those that presently flourish in the United States.10 Either way, she is able to make some assessment of the safety of impregnation before attempting to conceive internally. Reproduction with the use of assisted (ie, non-sex-based or "artificial") insemination is safer if the process is supervised. Australia has strict regulations for medically assisted insemination that compel screening for infectious disease. Because of the possibility of viral contamination it is mandatory to store donated semen for a minimum six months before use, pending repeat testing of the donor. Semen from anonymous donors can already be bought on the Internet; although nominally for purchase by medical practitioners, advertisements are targeted to potential recipients. The chief hazard with modern, anonymous sperm donation, especially among women not in a heterosexual relationship, and irrespective of the material requirements for raising children, is the lack of a genetic father to identify to the inevitably inquisitive child or children who result.11 Children who have been adopted are winning the right to identify their biological parents in country after country, and it is likely that the same rights will be won by the children of donated sperm, eggs and embryos. Some practitioners in the field of infertility medicine, myself included,11 have chosen to medically facilitate conceptions with donated gametes only when the intending donor is willing to be made known, and preferably to take some part in the child's extended family. Among sexually reproducing species, the power of choice of mate for the purpose of having offspring of wanted or optimal phenotypic characteristics is probably as ancient as copulation.12 It remains the most potent force for "eugenic" reproduction and is as natural as sex itself, no doubt moving from the subconscious to the conscious in much human reproductive decision making. Yet the vagaries of Mendelian inheritance and homologous recombination mean that a couple's offspring will still manifest wide variation. "Wouldn't it be good if [she/he] had your [this] and my [that]!" we say. And then, as night follows day, we laugh, "But maybe not so good with your that and my this!". At least, within the context of the mate they have chosen, most couples, most of the time, are happy to leave the rolling of the recombining chromosomes to chance. Conception need not be internal for a woman to reproduce. Developed to overcome infertility caused by destruction of the normal site of conception (the fallopian tubes), by the mid-1980s the certainty conferred by in-vitro fertilisation (IVF) had become proper practice for overcoming many other causes of infertility.13 Through embryo biopsy and molecular DNA testing of an embryonic cell or cells, IVF is also used for the detection of genetic abnormalities before implantation.14 Designer babies? Not quite. Genetic selection for certain traits within a family is not a blank canvas upon which any gene can be placed. To extend the metaphor, the palette cannot for the foreseeable future be broader than the prospective parents' particular genes; assortment is the variable they might try to influence. Charles Darwin had 10 children to express the diversity of his and his chosen mate's genetic phenotypes -- a number considered impractical today by most modern Australian couples. If prospective parents have a strong enough conviction that their child would be better without the burden of a gene or genetic trait that could be stopped, they could choose for implantation only those fertilised eggs that do not bear the unwanted gene. It is hard to distil valid objections to exercising reproductive choice this way that are distinct from faith-based moral objections to IVF itself15 -- and objectors to IVF on moral grounds have long been in the minority in Australian society.16 Similarly, the use of IVF for sex selection -- a use anticipating genetic testing (with evidence to date in Western countries revealing that there is a slight excess in couples attempting to select a girl as their next baby17) -- comes down to the question of whether reproductive choices in pluralistic societies are to be made by politically compelled governments, by committees of paternalistic strangers, or by the people who will live with the consequences of their decision. Will IVF widely replace getting-pregnant-by-having-sex? IVF today accounts for more than 1% of all babies born in Australia.18 This number will increase. In real terms, the cost of IVF is falling. Nonetheless, there are reasons why its use will not rise inexorably. The community cannot be expected to subsidise all its personal uses19 and it will continue to be expensive compared with sex and impregnation; it will also continue to be inconvenient and uncomfortable. Sex and vulnerability Most animals copulate with the opposite sex only when the female is in oestrus and is susceptible to conception,20 but since prehistoric times humans, like dolphins and bonobo chimpanzees, have had sex for reasons other than reproduction. That this is in principle a natural and expected thing is evidenced by the moral sanction many communities and cultures confer upon sexual intercourse during pregnancy (when another pregnancy can hardly be the goal). Whatever the particular sexual act might be, morality in a sociobiological context will, it is to be hoped, centre more on the reasons for having sex with the particular other person involved (if there is such a person). When we have sex there is a moral distinction between sex for the expression of love, promotion of fidelity, and mutual sexual relief or fun, on the one side, and the less virtuous motives of domination, emotional entrapment or abuse,9,20 on the other. Sex is inseparable from personal vulnerability and will remain so, and it is in the sharing or exploitation of personal vulnerability that its perennial power for causing good or harm resides. In my opinion, the social challenge for sex in the new millennium is at once to clarify the separate harms and benefits of impregnation, of reproduction, and of having sex with someone. We need to acknowledge and appreciate the differences, and, when the good outweighs the harm, or when the harm remains imaginary rather than based on evidence, we need to grow comfortable with and to give credence and legitimacy to the unorthodox. In our modern society we have both an earlier age at puberty and a later age considered suitable for parenthood. Whether it is advice to be comfortable sharing a toothbrush before accepting impregnation, or to regard virginity as lost only when sex has been unprotected from impregnation, the chasm that has opened between sex and reproduction, and into which our blinking adolescents stumble, needs a paradigm more understanding than abstinence or furtiveness. The singular, responsible satisfaction to be had from mucosal intimacy when sex, impregnation and reproductive intent all come together might or might not be slightly rarer in 2099 than 1999, but it will have lost none of its power to bond a human relationship. References Forrest BD. Women, HIV, and mucosal immunity. Lancet 1991; 337: 835-836. Jansen RPS. Bioethics and the spermatozoon. In: Grudzinskas JG, Yovich JL, editors. Cambridge Reviews in Reproduction. Gametes -- the spermatozoon. Cambridge: Cambridge University Press, 1995: 282-306. Ball RY, Scott N, Mitchinson MJ. Further observations on spermiophagy by murine peritoneal macrophages in vitro. J Reprod Fertil 1984; 71: 221-226. Lavitrano M, French D, Zani M, et al. The interaction between exogenous DNA and sperm cells. Mol Reprod Dev 1992; 31: 161-169. Chaykin S, Watson JG. Reproduction in mice: spermatozoa as factors in the development and implantation of embryos. Gamete Res 1983; 7: 63-73. Bellinge BS, Copeland CM, Thomas TD, et al. The influence of patient insemination on the implantation rate in an in vitro fertilization and embryo transfer program. Fertil Steril 1986; 46: 252-256. Duenhoelter JH, Jimenez JM, Baumann G. Pregnancy performance in patients under fifteen years of age. Obstet Gynecol 1975; 46: 49. Serhal PF, Craft IL. Oocyte donation in 61 patients. Lancet 1989; I: 1185-1187. Greer G. Raped women in refugee camps. In: The madwoman's underclothes. Essays and occasional writings 1968-85. London: Pan Books, 1987: 108-110. Jansen R. IVF and reproductive genetics in 1999: biology, business, ethics and sociology. In: Jansen R, Mortimer D, editors. Towards reproductive certainty. Fertility and genetics beyond 1999. London: Parthenon, 1999: 5-7. Jansen RPS. Reproductive medicine and the social state of childlessness. Med J Aust 1997; 167: 321-323. Jansen RPS. Bioethics and the oocyte: reproductive choice. In: Grudzinskas JG, Yovich JL, editors. Cambridge reviews in reproduction. Gametes -- the oocyte. Cambridge: Cambridge University Press, 1995: 396-427. Jansen R. The clinical impact of in-vitro fertilization. Part 1. Results and limitations of conventional reproductive medicine. Med J Aust 1987; 146: 342-353. Jansen R. Getting pregnant. A compassionate resource for overcoming infertility. Sydney: Allen & Unwin, 1997; 302-308. Jansen RPS. Evidence-based ethics and the regulation of reproduction. Hum Reprod 1997; 12: 2068-2075. Brumby M. Australian community attitudes to in-vitro fertilization. Med J Aust 1983; ii: 650-653. Statham H, Green J, Snowdon C, France-Dawson M. Choice of baby's sex. Lancet 1993; 341: 564-565. Hurst T, Shafir E, Lancaster P. Assisted conception in Australia and New Zealand 1997. Sydney: AIHW National Perinatal Statistics Unit, 1999; 1. Jansen R. The clinical impact of in-vitro fertilization. Part 2. Regulation, money and research. Med J Aust 1987; 146: 362-366. Greer G. Seduction is a four-letter word. Playboy 1973; January: 80-228. Authors' details University of Sydney, Sydney, NSW. Robert P S Jansen, Clinical Professor, Department of Obstetrics and Gynaecology, and Medical Director, Sydney IVF. Reprints will not be available from the author. Correspondence: Professor R S Jansen, Sydney IVF, 4 O'Connell Street, Sydney, NSW 2000. Make a comment

Research Hypertension in pregnancy: maternal and fetal outcomes according to laboratory and clinical features Mark A Brown and Megan L Buddle MJA 1996; 165: 360-365 Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Sexual health Abstract Objectives: To determine the predictive value of clinical and laboratory parameters for maternal and fetal complications in pregnant women with hypertension. Design: Prospective data collection. Setting: Two primary referral hospitals in the southern suburbs of Sydney between March 1987 and July 1994. Subjects: 1183 pregnant women with hypertension managed conjointly by a physician and obstetrician. Intervention: Uniform management protocol, plus antihypertensive medications if systolic blood pressure was persistently ≥ 160 mmHg and/or diastolic blood pressure ≥ 90 mmHg. Main outcome measures: Maternal and fetal complications, as defined by the Australasian Society for the Study of Hypertension in Pregnancy Consensus Statement. Results: Of 825 women with pre-eclampsia (502 mild; 323 severe), univariate analysis showed that hyperuricaemia, proteinuria and severe hypertension were significantly associated with a higher rate of maternal and fetal complications. In multivariate analyses without confounders, only primiparity, low serum albumin levels and absence of diabetes were significantly associated with severe pre-eclampsia. Severe pre-eclampsia, high haemoglobin levels and low platelet count were associated with higher rates of small-for-gestational-age babies, but only low serum albumin levels were associated with increased perinatal mortality rates. Low birthweight was associated with severe hypertension and severe pre-eclampsia. Conclusions: Simple clinical and laboratory parameters are useful predictors for maternal and fetal outcomes in pregnancies complicated by hypertension. Introduction Hypertensive disorders in pregnancy are common and their incidence appears to be increasing.1 These disorders comprise hypertension de novo in pregnancy (variably called pre-eclampsia, gestational or transient hypertension), and chronic forms of hypertension (essential and secondary hypertension), and have multiple modes of clinical presentations. With the current emphasis on outpatient management of pregnant women with non-proteinuric hypertension,2 clinicians require readily available clinical and laboratory parameters as indicators of the likely outcome of pregnancies complicated by hypertension. Such information is often difficult to obtain because of the selective nature of cases and complications reported by high-risk tertiary-care obstetric units, and is confounded by the varying treatments given to pregnant women before referral.3,4 Our study examined prospectively the maternal and fetal outcomes in women with hypertension in pregnancy, and the associated clinical and laboratory features. In particular, we sought to determine whether complications were greater if the woman had hyperuricaemia, severe hypertension and/or proteinuria, was nulliparous, or presented with hypertension early in the pregnancy. We also sought to determine which clinical and laboratory features were associated with severe pre-eclampsia. Methods The study group consisted of all pregnant women with hypertension who were referred by their obstetrician to one physician (M A B) at primary referral hospitals (St George or Hurstville community hospitals) in Sydney between March 1987 and July 1994. Indications for referral were: Hypertension failing to settle after overnight rest in hospital, or repeated measurement in a day-only unit; The presence of proteinuria or other abnormal urinalysis, abnormal biochemistry (serum electrolytes and creatinine levels, liver function tests) or thrombocytopenia; Recurrent admissions for hypertension; or A suspected secondary cause for hypertension. The definitions, classifications and complications of hypertension in pregnancy used in our study were those of the Australasian Society for the Study of Hypertension in Pregnancy (ASSHP) (Boxes 1 and 2).5 The maternal biochemical and haematological data used in our analysis were those recorded immediately before delivery. Complications were those having occurred by the time of discharge from hospital or by the postpartum check-up (after three months). Each patient's management was overseen by one physician (M A B) in conjunction with the patient's obstetrician. A standardised management protocol was followed by all staff during the course of this study (Box 3). Statistical analysis All data were stored in a database program (iBANK) and analysed using Minitab statistical package6 and BMDP statistical software.7For initial bivariate analyses, the frequency of adverse events within groups was tested by χ2 analysis and, where significant, by 2 x 2 contingency tables. Biochemical and haematological indices and birthweights were compared using Student's t tests, and significance assessed using Hochberg's method for interpreting multiple comparisons. The maternal-outcome variable was severity of pre-eclampsia. Logistic regression analysis was used to analyse the following variables as predictors of severe pre-eclampsia: parity; gestation at presentation; age; plasma uric acid level; serum albumin, haemoglobin and haematocrit levels; and diabetes. Proteinuria, platelet count and serum creatinine levels were not analysed because abnormalities of these form part of the diagnosis of severe pre-eclampsia. Fetal-outcome variables were birthweight, small-for-gestational-age (SGA) and perinatal mortality (PNM). Each of the following variables was analysed as a predictor of poor fetal outcome: maternal complications, age, parity, diabetes, gestation at presentation and laboratory data. Multiple regression analysis was used for birthweight and logistic regression analysis for SGA and PNM. For regressions, backward elimination was used until all remaining predictors were statistically significant (P < 0.05). Results Clinical details From March 1987 to July 1994, 1183 pregnant women with hypertension fulfilled the criteria for referral to a physician (M A B) and were entered into the study, representing 6.7% of all confinements at the two hospitals. During this period, 2121 women were documented in hospital records as having hypertension in pregnancy, representing 12% of all confinements. There were 825 women (70%) with pre-eclampsia (mild, 502; severe, 323), 82 (7%) with superimposed pre-eclampsia, 223 (19%) with essential hypertension, and 53 (4%) with secondary hypertension (predominantly renal disease). Oral antihypertensive medications were given to 563 women (48%), additional parenteral antihypertensives were required by 281 (24%), and 339 (29%) received no antihypertensive medications. Thirteen women (1%) received "prophylactic" low-dose aspirin. Five women (0.4%) required dialysis during or after pregnancy and four women (0.3%) had convulsions. Seventy-three women (6%) had pre-existing or gestational diabetes mellitus. Of the 1242 babies born to the women in the study, there were 15 perinatal deaths (12 per 1000 hypertensive pregnancies). There was one maternal death (0.08%) in a 29-year-old woman who presented at 29 weeks' gestation with severe pre-eclampsia and who delivered immediately and died unexpectedly the next day. Despite autopsy, the cause of death was not established. Predictors of outcomes in women with pre-eclampsia Univariate analysis Hyperuricaemia was significantly associated with higher rates of all maternal complications and SGA babies and babies with lower average birthweights than normal plasma uric acid levels (Box 4). Severe hypertension was significantly associated with higher maternal complication rates and earlier gestation at delivery than mild hypertension (Box 4). This group of women had babies of a lower average birthweight, a higher proportion of SGA babies and a higher perinatal mortality rate. Proteinuria was significantly associated with similar maternal and fetal complication rates as severe hypertension, and the proportion of SGA babies was similar to non-proteinuric hypertension (Box 4). Parity did not affect maternal complication rates, except for a higher prevalence of severe hypertension and liver disease in nulliparae (Box 5). Early gestation at presentation with hypertension (at or before 32 weeks' gestation) was significantly associated with a higher prevalence of proteinuria than later presentation (Box 5). Multivariate analysis Severe pre-eclampsia was associated with low serum albumin (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.90-0.97; P = 0.0001), primiparity (OR, 0.51; 95% CI, 0.33-0.79; P = 0.002) and the absence of diabetes (OR, 0.21; 95% CI, 0.05-0.93; P = 0.04). SGA was associated with severe pre-eclampsia (OR, 2.5; 95% CI, 1.6-3.9; P = 0.0001), high maternal haemoglobin levels (OR, 3.7; 95% CI, 1.1-12.8; P = 0.04) and low platelet counts (OR, 1.4; 95% CI, 1.1-1.8; P = 0.02). Birthweight was positively associated with gestation at presentation (regression coefficient [β], 41; standard error [SE], 5; P < 0.0001) and serum albumin levels (β, 28; SE, 5; P < 0.0001) and inversely associated with severe hypertension (β, 2193; SE, 69; P < 0.005) and severe pre-eclampsia (β, 2311; SE, 60; P < 0.0001). Perinatal mortality was associated only with low serum albumin levels (OR, 0.88; 95% CI, 0.82-0.95; P < 0.0003), but there were too few perinatal deaths to support a useful formal analysis. Outcomes in women with all forms of hypertension in pregnancy Box 6 shows the maternal and fetal outcomes in women with the different forms of hypertension in pregnancy. Maternal and fetal outcomes were better for women with essential hypertension than for the other groups. Twenty-seven per cent (or 10% if proteinuria was included in the diagnosis) of women with essential hypertension developed superimposed pre-eclampsia. Women with superimposed pre-eclampsia delivered their babies earlier, had babies with lower average birthweights, significantly more SGA babies and significantly higher rates of all maternal complications than women with essential hypertension alone. Women with secondary (predominantly renal) hypertension had similar maternal and fetal outcomes to women with superimposed pre-eclampsia (data available from author). Discussion In our prospective study, there was uniform management of all women with hypertensive disorders in pregnancy. As the database excluded very mild cases of hypertension in pregnancy, an inherent bias exists, but our study provides a general estimate of fetal and maternal outcomes for women with hypertension managed in primary referral hospitals. During the study period, 12% of all confinements were complicated by hypertension, which is either similar to or higher than previous reports.8-11 Hjertberg et al. noted a 5% incidence of hypertension in pregnancy, of whom 83% had hypertension de novo in pregnancy.12 In our study, 70% of women had pre-eclampsia (hypertension de novo in pregnancy), 19% had essential hypertension alone, 7% had superimposed pre-eclampsia, and 4% had a renal or other secondary cause. These results are similar to those from a smaller study in a tertiary referral unit.13 When analysed separately, hyperuricaemia, proteinuria and severe hypertension were associated with higher rates of all maternal and fetal complications, while parity was associated with severe hypertension and liver disease. Presentation before 32 weeks' gestation impacted negatively on fetal outcome. We have reported previously on the adverse impact of proteinuria on maternal and fetal outcomes.14 Hyperuricaemia is an established marker of severe pre-eclampsia, correlating histologically with the severity of renal lesions,15 and clinically with adverse fetal outcomes.16 We found that hyperuricaemia, when considered alone, was associated with higher maternal complication rates and fetal growth retardation, but, with multivariate analysis, was not a significant predictor of adverse maternal or fetal outcomes. Hyperuricaemia remains a useful marker of pre-eclampsia, but women with normal serum uric acid levels and pre-eclampsia may still develop complications. Severe hypertension was confirmed by multivariate analysis to be associated with low birthweight babies, and, in univariate analysis, with a higher incidence of all fetal complications and a higher incidence of SGA babies. Therefore, the more severe the hypertension, the more the likelihood of fetal as well as maternal complications. Pre-eclampsia has long been considered a disorder of primigravidae.17 However, it is clear that pre-eclampsia does occur in second or subsequent pregnancies (particularly following a change of partner); in our study, approximately two-fifths of the women with pre-eclampsia were parous women. Parous women had a lower incidence of severe hypertension and liver disease when compared with nulliparae, but there were no other differences in outcomes between these groups. Therefore, equal risk to the fetus should be assumed in both groups of women once hypertension has developed in the second half of pregnancy. The gestation at presentation in pre-eclampsia influences fetal outcome because of the likelihood of early delivery, but we are unaware of any prospective studies that relate gestation at presentation to maternal complication rates. Apart from proteinuria, maternal complication rates for women presenting before 33 weeks' gestation in our study were similar to those who presented later. Two retrospective studies have reported a higher incidence of maternal complications in women with pre-eclampsia of early onset.18,19 Our patients presenting early with pre-eclampsia had milder disease than that reported by Sibai et al.20 As expected, the earlier the gestation with pre-eclampsia the lower the birthweight (because gestation did not proceed as far as those presenting later), but the likelihood of having an SGA baby was not increased. Although maternal diabetes was associated with a lower risk of severe pre-eclampsia, only 6% of our study population had diabetes. Therefore, it should not be assumed that diabetes protects pregnant women against severe pre-eclampsia. The consistent relationship between low serum albumin levels and adverse maternal and fetal outcomes was independent of proteinuria and implies that hepatic albumin synthesis is altered in severe pre-eclampsia. The association between high maternal haemoglobin levels and SGA babies presumably reflects a reduced plasma volume and haemoconcentration, which is associated with poor fetal growth.21 In conclusion, for women with pre-eclampsia, the traditional clinical markers of proteinuria, parity and severe hypertension remain useful clinical indices of maternal risk, while severe pre-eclampsia, severe hypertension, elevated haemoglobin and low serum albumin levels portend increased fetal risk. Acknowledgements We wish to thank the obstetricians of St George and Hurstville community hospitals, Professor J A Whitworth, Ms Jodie Wilkinson and Dr M Jones (Intstat Australia Pty Ltd). References Crawford JS. Epidemic pre-eclampsia. Lancet 1987; 1: 329-330. Tuffnell DJ, Lilford RJ, Buchan PC, et al. Randomised controlled trial of day care for hypertension in pregnancy. Lancet 1992; 339: 224-227. Horvath JS, Korda A, Child A, et al. Hypertension in pregnancy. A study of 142 women presenting before 32 weeks' gestation. Med J Aust 1985; 143: 19-21. Clarke M, Mason ES, Macvicar J, Clayton DG. Evaluating perinatal mortality rates: effects of referral and case mix. BMJ 1993; 306: 824-827. Australasian Society for the Study of Hypertension in Pregnancy. Consensus Statement on Management of Hypertension in Pregnancy: Executive Summary. Med J Aust 1993; 158: 700-702. Minitab [computer program], version 9.1. Pennsylvania State College: Minitab Inc, 1993. BMDP [computer program]. Berkeley, Calif: University of California, 1990. Martikainen AM, Heinonen KM, Saarikoski SV. The effect of hypertension in pregnancy on fetal and neonatal condition. Int J Gynaecol Obstet 1989; 30: 213-220. Andrews WW, Cox SM, Sherman ML, Leveno KJ. Maternal and perinatal effects of hypertension at term. J Reprod Med 1992; 37: 73-76. Safflas AF, Oldson DR, Franks AL, et al. Epidemiology of pre-eclampsia and eclampsia in the United States, 1979-1986. Am J Obstet Gynecol 1990; 163: 460-465. Pietrantoni M, O'Brien WF. The current impact of the hypertensive disorders of pregnancy. Clin Exp Hypertens 1994; 16: 479-492. Hjertberg R, Bellrage P, Hanson U. Conservative treatment of mild and moderate hypertension in pregnancy. Acta Obstet Gynecol Scand 1992; 71: 439-446. Horvath JS, Phippard A, Henderson-Smart D, et al. High risk hypertensive pregnancies: maternal and foetal outcome. Clin Exp Hypertens Pregnancy 1983; B2: 21-28. Brown MA, Buddle ML. The importance of non proteinuric hypertension in pregnancy. Hypertens Pregnancy 1995; 14: 57-65. Pollak VE, Nettles JB. The kidney in toxemia of pregnancy: a clinical and pathologic study based on renal biopsies. Medicine (Baltimore) 1960; 39: 469-526. Redman CWG, Beilin LJ, Bonnar J, Wilkinson PH. Plasma urate measurements in predicting fetal death in hypertensive pregnancy. Lancet 1976; 2: 1370-1373. Chesley LC. Diagnosis of pre-eclampsia. Obstet Gynecol 1985; 65: 423-425. Sibai BM, Taslimi M, Abdella TN, et al. Maternal and perinatal outcome of conservative management of severe pre-eclampsia in midtrimester. Am J Obstet Gynecol 1985; 152: 32-37. Railton A, Allen DG. Management and outcome of pregnancy complicated by severe pre-eclampsia of early onset. S Afr Med J 1987; 72: 608-610. Sibai BM, Mercer BM, Schiff E, Friedman SA. Aggressive versus expectant management of severe pre-eclampsia at 28 to 32 weeks' gestation: a randomized controlled trial. Am J Obstet Gynecol 1994; 171: 818-822. Brown MA, Zammit VC, Mitar DM. Extracellular fluid volumes in pregnancy-induced hypertension. J Hypertens 1992; 10: 821-829. (Received 9 Oct 1995, accepted 13 May 1996) Authors' details Departments of Medicine, Renal Medicine and Obstetrics, St George and Hurstville community hospitals, University of NSW. Mark A Brown, MB BS, FRACP, MD, Associate Professor of Medicine; Megan L Buddle, SRN, Hypertension Unit Registered Nurse. No reprints will be available. Correspondence: Associate Professor M A Brown, Department of Renal Medicine, St George Hospital, Kogarah, NSW 2217. E-mail: "nest::brown"ATdodo.ssahs.unsw.edu.au 1: ASSHP classifications and definitions of hypertension in pregnancy Hypertension: A sitting systolic blood pressure (BP) ≥ 140 mmHg and/or diastolic BP (phase IV Korotkoff sound) ≥ 90 mmHg, or a rise in systolic BP of ≥ 25 mmHg and/or diastolic BP ≥ 15 mmHg from first-trimester BP (two readings taken six hours apart). Proteinuria: ≥ 300 mg/day (24-hour urine collection) or persistently (over two or more days) ≥ 2+ protein (1 g/L) on urinalysis (dipstick testing). As urinalysis was performed daily, non-proteinuric hypertension that progressed to proteinuric hypertension was always detected. Hyperuricaemia: Plasma uric acid level > 0.35 mmol/L. Pre-eclampsia: The development of hypertension after 20 weeks' gestation in a woman with no known history of hypertension or renal disease and whose blood pressure (BP) was normal in the first half of the pregnancy and returned to normal after delivery: (i) mild pre-eclampsia: hypertension only; (ii) severe pre-eclampsia: hypertension and evidence of maternal organ dysfunction (see Maternal complications, Box 2). Essential hypertension: Hypertension in the first half of pregnancy (often occurring before pregnancy) without a demonstrable secondary cause, or the appearance of hypertension in the second half of pregnancy in a woman whose BP failed to return to normal within three months after delivery. Superimposed pre-eclampsia: The development of proteinuria and/or hyperuricaemia in the second half of pregnancy in a woman with essential hypertension. Secondary hypertension: To exclude a secondary cause of hypertension, all women had serum potassium levels measured and had urinalysis, microscopy and a clinical examination; urinary catecholamines and renal ultrasound were performed in selected cases. Within this group, superimposed pre-eclampsia was not diagnosed as a separate entity as it was too difficult to ascertain whether changes (e.g., increasing proteinuria) reflected superimposed pre-eclampsia or progression of the underlying (usually renal) disease. ASSHP = Australasian Society for the Study of Hypertension in Pregnancy.5 Back to text 2: ASSHP complications of hypertension in pregnancyMaternal complications:(i)Severe hypertension: Blood pressure (BP) ≥ 170 mmHg systolic and/or ≥ 110 mmHg diastolic;(ii)Proteinuria (Box 1);(iii)Haematological abnormalities: haemolysis (haemoglobin < 110g/L, with reticulocytosis, fragments) or thrombocytopenia (< 150 x 109/L platelets);(iv)Renal impairment: serum creatinine level ≥ 0.10 mmol/L;(v)Liver disease: elevated serum aspartate aminotransferase level > 40 IU/L, with or without severe epigastric pain;(vi)Neurological disturbances: visual scotoma; severe headaches with hyperreflexia; hyperreflexia with sustained clonus (> 3 beats). Fetal complications:(i)Small-for-gestational-age (SGA): birthweight below the 10th centile for gestation, corrected for sex;(ii)Perinatal mortality (PNM): stillbirths and neonatal deaths per 1000 hypertensive pregnancies. ASSHP = Australasian Society for the Study of Hypertension in Pregnancy.5Back to text 3: Management protocol during pregnancy Maternal complications: Blood pressure (BP) measurements six times per day; Fetal cardiotocograph recordings on alternate days (or more often if clinically indicated); Daily urinalysis; Biochemistry and haematological testing at least twice weekly; Bedrest if there is evidence of intrauterine fetal growth retardation, or maternal neurological features or severe hypertension. Antihypertensive therapy: Oral antihypertensive therapy (single agent or combinations) of oxprenolol, hydralazine, methyldopa, prazosin or nifedipine was instituted if the systolic BP was persistently > 160 mmHg or diastolic BP persistently > 90 mmHg after overnight bedrest in hospital. Parenteral antihypertensive therapy (sublingual nifedipine or intravenous hydralazine) was given for severe hypertension (Box 2). Convulsion prophylaxis (intravenous phenytoin followed by oral phenytoin) was used for women with neurological disturbances (Box 2). Indications for delivery. Delivery (by induction) was scheduled after 38 weeks' gestation if the BP remained stable and the cervix was favourable. Indications for delivery before 38 weeks' gestation were:5 Fetal compromise: premorbid (cardiotocographic) tracing of fetal heart rate or failure of fetal growth (assessed by doppler ultrasound). Inability to control maternal BP; Persistent neurological disturbances (see Box 2); Progressively rising liver enzyme or serum creatinine levels, or worsening thrombocytopenia. Women whose pregnancies could not be prolonged beyond 30 weeks' (and occasionally 32 weeks') gestation were sometimes transferred before delivery to a tertiary referral unit with neonatal intensive care facilities. Outcomes of this group were included in our analysis. Back to textFor box 4 click here 5: Maternal and fetal outcomes in women with pre-eclampsia (mild and severe) according to parity and gestation at presentation (see text for definitions). Data are percentages or means (standard deviation). Gestation at presentationNulliparae ParousP ≤ 32 wks> 32 wks Pn508317129696Age (years)27 (5)30 (5) < 0.0001*29 (5)28 (5)0.30Nulliparae (%)10000.0001*57630.20Gestation at presentation (weeks)36 (4)35 (6)0.00927 (7)37 (2)< 0.0001*Gestation at delivery (weeks)38 (3)38 (2) 0.8935 (4)38 (2)< 0.0001*Hyperuricaemia (%)61540.0456590.53Maternal complicationsSevere hypertension24%15%0.001*29%19%0.008Thrombocytopenia11%8%0.1011%10%0.75Proteinuria21%16%0.0931%17%0.003*Renal insufficiency8%5%0.089%7%0.27Liver disease12%6%0.005*15%9%0.04Neurological13%10%0.4116%11%0.09Laboratory dataPlasma creatinine (mmol/L).07 (.04).07 (.02).18.08 (.08)0.07 (.02) 0.51Plasma uric acid (mmol/L).40 (.20).37 (.04) .01.38 (.09)0.39 (0.17)0.66Plasma albumin (g/L)33 (5)34 (5) .3431 (8)34 (4)0.002*Haemoglobin (g/L)119 (23)122 (16) .03117 (37)121 (15)0.20Haematocrit (%)35.1 (5.5)35.9 (5.6) .1033.7 (8.7)35.7 (4.7)0.02Platelets (x 109/L)223 (82)232 (82) .11206 (95)230 (79)0.009*Fetal complicationsSGA (%)17210.1724180.10PNM (per 1000)1730.06544< 0.0001*Birthweight (g)2984 (701)2985 (694) 0.982312 (960)3105 (561)< 0.0001* * Statistically significant . SGA = small-for-gestational-age. PNM = perinatal mortality. Back to text 6: Maternal and fetal outcomes in women with different forms of hypertension in pregnancy (ASSHP classifications). Data are percentages or means (standard deviation). Pre-eclampsiaEssential hypertension Superimposed pre-eclampsiaP*n82523382Age (years)28 (5)30 (530 (5)> 0.0001†Nulliparae (%)6237560.290.002†Gestation at presentation (weeks)35 (5)26 (10)28 (10) < 0.0001†0.17Gestation at delivery (weeks)38 (3)38 (2)36 (1)0.0007†< 0.0001†Hyperuricaemia (%)581683< 0.0001†0.0001†Maternal complicationsSevere hypertension21%13%38%0.0005†< 0.0001†Thrombocytopenia10%1%16%0.11< 0.0001†Proteinuria19%035%0.0005†< 0.0001†Renal insufficiency7%09%0.62< 0.0001†Liver disease10%1%11%0.79< 0.0001†Neurological12%3%20%0.06< 0.0001†Laboratory dataPlasma creatinine (mmol/L)0.07 (0.04)0.06 (0.02)0.07 (0.02)0.78< 0.0001†Plasma uric acid (mmol/L)0.39 (0.16)0.32 (0.25)0.46 (0.35)0.090.002†Plasma albumin (g/L)33 (5)35 (6)33 (5)0.810.04Haemoglobin (g/L)120 (20)119 (14) 117 (17)0.140.52Haematocrit (%)35.4 (5.5)35.1 (4.0) 34.7 (5.4)0.290.64Platelets (x 109/L)226 (82)256 (68) 235 (78)0.360.03Fetal complicationsSGA (%)199280.20< 0.0001†PNM (per 1000)129120.930.80Birthweight (g)2984 (701)3260 (652) 2795 (935)0.080.0001†* Significance of difference between outcomes for women with pre-eclampsia and superimposed pre-eclampsia (and for women with essential hypertension and superimposed pre-eclampsia). †Statistically significant. SGA = small-for-gestational-age. PNM = perinatal mortality. ASSHP = Australasian Society for the Study of Hypertension in Pregnancy.5 Back to text

Mark A Brown · Megan L Buddle

Medicine and the Community Assisted reproduction: a reassuring picture Many couples seek solutions to problems of infertility by using assisted reproduction techniques. Despite very different beginnings, children conceived after donor insemination, ovum donation, in-vitro fertilisation or gamete intrafallopian transfer show no adverse long term effects, either physically or psychosocially. Gabor T Kovacs MJA 1996; 164: 628-630 Introduction - Donor insemination - Ovum donation - Issues of genetic identity - In-vitro fertilisation - Intracytoplasmic sperm injection (ICSI) - Reproductive technology and the risk of cancer - Conclusions - References - Authors' details - - More articles on Sexual health Introduction A 1995 report on assisted conception from the Australian Institute of Health and Welfare showed that there were over 2300 births after conception by in-vitro fertilisation (IVF) and gamete intrafallopian transfer (GIFT) in 1993, and that about 1% of all births in Australia are a result of these techniques.1 Between 1980 and 1993, more than 15 000 babies were born in Australia after conception by IVF and GIFT.1 Since the mid-1970s, several hundred more have been born each year after artificial insemination with donor sperm. As more families are using assisted reproduction techniques, the long term outcome of these children and their families has become an important issue. Donor insemination The first investigation of long term outcomes after assisted reproduction was performed on 54 children born after conception by donor sperm in Tokyo in 1968.2 These children, aged up to 11 years, were not inferior in measures of body weight and length or in intelligence and development quotients when compared with a control group of children conceived naturally. Over the next decade, the same conclusions were reached when the study was expanded to include 133 children.3Similar results for psychomotor development and psychological adjustment in children born through donor insemination programs were found in two early 1980s retrospective French studies of 30 and 75 families,4,5 and in a 1990 American study of 362 families.6 The first assessment of families who had had children by donor insemination in Australia was a retrospective study in 1982 that showed no major obstetric, paediatric or emotional problems in 50 children aged between one and three years.7 Researchers at the Prince Henry Institute in Melbourne in 1993 did the first controlled study of the psychosocial development of children conceived by donor insemination.8 Twenty-two children conceived by this technique and aged from six to eight years were compared with matched controls (20 children conceived naturally and 10 adopted children). Psychomotor scores derived from the Achenbach Child Behaviour Checklist showed no significant difference between the three groups of children.8 In a Sydney study by Durna et al., 76% of 276 couples thought that having had a child by donor insemination had a positive personal effect and less than 1% had regrets.9 Forty-seven per cent felt their marriage had improved, which is similar to the 54% seen in an American study.6 Marriage breakdown was reported at 3.6%, which is less than the rate for the general population. Durna et al. concluded that prospective couples could be reassured that having a child by donor insemination can have positive psychosocial effects on their relationships. The most detailed study of families with a child conceived by assisted reproductive technology was by Golombok et al., who studied 45 families with a child by donor insemination, 41 families with a child by IVF, 55 families with an adopted child and 43 control families.10 Assessments involving interviews and questionnaires were carried out on children aged from four to eight and their parents to determine the children's emotions, behaviour and relationships, and the parents' psychological state and quality of parenting. The quality of parenting for children conceived by assisted reproductive technology appeared superior to that of naturally conceived children. There were no significant differences between children conceived by donor insemination and children conceived by IVF. Ovum donation A survey of donor oocyte clinics worldwide in 1991 identified just over 200 such pregnancies.11 Thirty-six couples who conceived children using donor oocytes in Melbourne between 1983 and 1991 unanimously agreed that they would recommend ovum donation.12 However, as the technique of ovum donation is a more recent development, the number of studies are limited and further studies are needed to assess long term outcome. Issues of genetic identity Of increasing concern is the issue of genetic identity. What are the psychosocial effects on a child conceived from donated gametes who knows about his or her true biological origins? The issue may not be resolved for several years as open discussion about donor insemination has only recently become acceptable. In the study by Durna et al., 21% of couples were concerned about telling their child about donor insemination.9A 1995 study by Daniels et al. found considerable disagreement and debate about whether to tell their child among 58 couples who had conceived a child through donor insemination at the Dunedin Infertility Clinic (New Zealand).13 Controlled studies are required to compare children who know their biological origins with children who do not. In-vitro fertilisation There are no reports that have followed up children conceived by GIFT. The first cohort of IVF children were born in Australia. In an initial follow-up report from Melbourne in 1985, 52 children conceived by IVF were assessed developmentally at birth and at 10 months, and 33 had a psychosocial assessment between one and three years of age.14 The principal findings were the caesarean section rate was much higher (37%); the rate of premature births was four times the expected rate; and the number of very low birthweight children and twins were 10 times more than that expected for children conceived naturally. Scores on the Bayley Scales of Infant Development fell within normal range. Although this was an uncontrolled study and there was an increased rate of obstetric intervention, the authors concluded that these families did not have an increased rate of psychosocial or developmental problems. Similar results were found in a Perth study in 1986 in which 20 children conceived by IVF were reviewed a year after birth.15 In a controlled American study of 83 children conceived by IVF and 93 controls, physical examination, neurological and developmental examination, echocardiography, electrocardiography and abdominal and cranial ultrasound examination were performed on each child.16 There was no significant difference in mental or psychomotor development. However, in a small but controlled French study, there was a significant difference in the relationship between mothers and their children conceived through IVF compared with infertile women having ovulation induction and a control group of mothers who had conceived naturally.17 The largest controlled study on outcomes after IVF was based on 314 children conceived through IVF and 150 matched controls in Melbourne.18 Families were assessed when the children were two years of age and underwent tests such as the Short Temperament Questionnaire for Toddlers, Family Environment Scale, General Health Questionnaire, Dyadic Adjustment Scale, Interview Schedule for Social Interaction and the Monash Family Interview. The authors found that both the cognitive and motor development of children conceived through IVF fell within the normal range, and that there was no difference in parental concerns or child care patterns between the IVF parents and the control parents, and no difference in neonatal problems or physical outcomes (including disabilities or congenital malformations). However, there was a high caesarean section rate. Intracytoplasmic sperm injection (ICSI) In ICSI , a single sperm is injected into the cytoplasm of the ovum, under microscopic control. It is used in cases of severe male subfertility. A recent Dutch study reported five cases of sex chromosomal anomalies among 15 fetuses conceived after ICSI and tested by chorionic villus sampling.19 However, this sample size was too small to draw any clinically relevant conclusions. In contrast, the Brussels group who developed the ICSI technique in 1991 reported on 669 children born by mid-1995 who had been conceived by this method.20 Of the 491 who had had prenatal karyotyping, 479 (97.6%) had a normal karyotype and 12 (2.5%) had an abnormal karyotype (half of these were benign structural aberrations). Major congenital malformations were reported in 18 (2.7%) of the 669 children born following ICSI. A review of Australian and New Zealand microinsemination data up to 1993 found nine major abnormalities among 220 fetuses but no chromosomal anomalies.1 The National Perinatal Statistics Unit is assessing a larger cohort by collecting data for all ICSI pregnancies in Australia in 1994 and 1995 (P Lancaster, Director, AIHW National Perinatal Statistics Unit, Sydney, NSW, personal communication). Reproductive technology and the risk of cancer A recent retrospective study found no increased incidence of breast or ovarian cancer in 5564 women who had had ovarian stimulation as part of their infertility treatment compared with 4794 infertile couples.21 Conclusions In 1992, the National Health and Medical Research Council of Australia established a Working Party to examine the long term health effects on families who have had a child by assisted conception.22 After reviewing the literature, this Working Party asked more questions than it answered and recommended the continuation of long term studies of these families. No deleterious long term effects of reproductive technology have been shown in either the offspring or their families. It appears that families with a child conceived by donor insemination, IVF or GIFT do not have an increased risk of psychosocial or developmental problems compared with children conceived naturally. References Lancaster P, Shafir E, Huang J. Assisted conception in Australia and New Zealand 1992 and 1993. Australian Institute of Health and Welfare and the Fertility Society of Australia. Sydney: AIHW, 1995. Iizuka R, Sawada Y, Nishina OM. The physical and mental development of children born following artificial insemination. Int J Fertil 1968; 13: 24-32. Mochimaru F, Sato H, Kobayaski T, Iizuka R. Physical and mental development of children born through AID. In: David G, Price WS, editors. Human artificial insemination and semen preservation. New York: Plenum Press, 1980: 277-282. Semenov G, Mises R, Bissery J. Attempt at follow-up of children born through AID. In: David G, Price WS, editors. Human artificial insemination and semen preservation. New York: Plenum Press, 1980: 474-477. Manuel C, Czyba J. Follow-up study on children born through AID. In: David G, Price WS, editors. Human artificial insemination and semen preservation. New York: Plenum Press, 1980: 467-474. Amuzu B, Laxova R, Sander S. Pregnancy outcome, health of children, and family adjustment after donor insemination. Obstet Gynecol 1990; 75: 899-905. Clayton CE, Kovacs GT. AID offspring. Initial follow-up study of 50 couples. Med J Aust 1982; 1: 338-339. Kovacs GT, Mushin D, Kane H, Baker HWG. A controlled study of the psychosocial development of children conceived following insemination with donor semen. Hum Reprod 1993; 8: 788-790. Durna EM, Bebe J, Leader LR, et al. Donor insemination: effects on parents. Med J Aust 1995; 163: 248-251. Golombok S, Cook R, Bish A, Murray C. Families created by the new reproductive technologies: quality of parenting and social and emotional development of the children. Child Dev 1995; 64: 285-298. King CM, Kovacs GT. Oocyte donation: survey of results. In: Oocyte Donation. Reprod Fertil Dev 1992; 4: 119-124. Munro J, Leeton J, Horsfall T. Psychosocial follow-up of families from a donor oocyte programme: an exploratory study. In: Oocyte Donation. Reprod Fertil Dev 1992; 4: 125-130. Daniels KR, Lewis GM, Gillett W. Telling donor insemination offspring about their conception: the nature of couples decision making. Soc Sci Med 1995; 40: 1213-1220. Mushin DN, Spensley J, Barreda-Hanson M. Children of invitro fertilization. Clin Obstet Gynecol 1985; 12: 865-876. Yovich JL, Parry TS, French NP, Grauaug AA. Development assessment of twenty in vitro fertilization (IVF) infants at their first birthday. J InVitro Fertil Embryo Transfer 1986; 4: 253-257. Marin N, Wirth F, Johnson DH, et al. Congenital malformations and psychosocial development in children conceived by in vitro fertilization. J Pediatr 1989; 115: 222-227. Raoul-Duval A, Bertrand-Servais, Frydman R. Comparative prospective study of the psychological development of children born by in vitro fertilization and their mothers. J Psychosom Obstet Gynaecol 1993; 14: 117-126. Halasz G, Munro J, Saunders K, et al. The growth and development of children conceived by IVF. Report to the Commonwealth Department of Health, Housing, Local Government and Community Services; Research and Development Grants Advisory Committee (RADGAC); and Victorian Health Promotion Foundation. Melbourne, Monash University Department of Psychological Medicine, 1993. Veld P, Brandenburg H, Verhoeff A, et al. Sex chromosomal abnormalities and intracytoplasmic sperm injection. Lancet 1995; 346: 773. Liebaers I, Bonduelle M, Legein J, et al. Follow-up of children born after intracytoplasmic sperm injection. In: Hedon B, Bringer J, Mares P, editors. Fertility and sterility: a current overview. New York: Parthenon, 1985: 409-412. Venn A, Watson L, Lumley J, et al. Breast and ovarian cancer incidence after infertility and invitro fertilisation. Lancet 1995; 346: 995-1000. National Health and Medical Research Council. Long term effects on women from assisted conception. Consultation document. Canberra: NHMRC, 1995. This article is based on a lecture presented at the 15th World Congress on Fertility and Sterility, Montpellier, France, 17-22 September 1995. Authors' details Department of Obstetrics and Gynaecology, Monash Medical School, Box Hill Hospital, Box Hill, VIC. Gabor T Kovacs, MD, FRACOG, Director. Chairman, IVF Directors Group, Fertility Society of Australia. No reprints will be available from the author.

Gabor T Kovacs

Endemic STDs in remote communities: the challenge for STD control High rates of STDs in Australian Aboriginal communities point to limitations in current surveillance and control methods MJA 1997; 166: 456 Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". - ©MJA1997 A recent MJA editorial recognised Australia's achievements in controlling sexually transmitted disease (STD), but emphasised that the necessary aim must be "striving to eliminate endemic disease".1 Two articles in this issue of the Journal2,3 highlight the problems in the path of this objective -- and some of the potential solutions. Our information on the extent of STD in the population is largely derived from a passive notification system. Sentinel sites that routinely screen their client population for STDs and community surveys supplement the data from notification systems. Sentinel surveillance for HIV is conducted at urban sexual health clinics and data are collated nationally by the National Centre for HIV Epidemiology and Clinical Research, but there is no national collection of sentinel data for STD outside sexual health clinics. Our understanding of the epidemiology of STD outside the cities and towns is incomplete. What you test for is what you see, and our passive notification systems may be blind to much STD in the community Nationally, notifications of gonorrhoea and syphilis have declined in recent years,4 but celebration may be premature. The community-based survey reported in this issue by Skov et al. demonstrates that our notification systems may not provide an accurate picture of STD distribution in Australia.2 Their study found a far higher rate of gonorrhoea and chlamydia than would have been expected from previous notification data. Notifications made as a result of their community screening were responsible for a significant part of the 59% increase in notifications of gonorrhoea in South Australia in 1995.5 What you test for is what you see, and our passive notification systems may be blind to much STD in the community. At present, notifications are more often received from communities that recognise STD as an important health issue. Thus, communities that act on their responsibility for sexual health and STD control run the risk of being denigrated because of their apparently high rates of STD, while other communities not active in sexual health may have similar or bigger problems that remain largely hidden. The problem of detecting cases of STD is also an issue in evaluating the extent of their complications, which often form the greatest burden of disease. As shown in the report by Mein and Bowden (page 464 of this issue of the Journal),3 this burden falls heavily upon women in Aboriginal communities. What is perhaps most alarming in their case review is that only 45% of patients admitted to a gynaecological ward with suspected pelvic inflammatory disease were tested appropriately for STD (by endocervical swab). The rates of infection calculated by Mein and Bowden are therefore only the minimum estimate of gonococcal and chlamydial infection in pelvic inflammatory disease. The effort to control STD in Aboriginal communities can be facilitated by using new technology. In particular, tests based on the polymerase chain reaction (PCR) can diagnose chlamydia and gonorrhoea from urine samples. Such samples can be collected and processed more easily than swabs, and the procedure is more acceptable to Aboriginal people. This application of PCR technology is still in its infancy, and there may be some interpretation problems. The PCR test detects DNA or RNA, but does not tell us if the material comes from an infectious organism or from non-infectious remnants of a resolving infection. Another problem is that PCR testing does not allow the determination of antibiotic sensitivity patterns. Sentinel surveillance activities (involving culture for gonorrhoea to determine trends in antimicrobial resistance) must continue so that control efforts are not frustrated by drug resistance. PCR technology can be used in two ways in STD control. Firstly, in community surveys, such as that described by Skov et al.2 This survey, a collaborative effort between Aboriginal and government health services, required considerable infrastructure and community consultation, which were facilitated by the TriState STD/HIV Project (funded by the Western Australian, South Australian, Northern Territory and Commonwealth health departments). The collaborative approach of the TriState STD/HIV Project offers a model for undertaking surveys of this nature. A second application is through increased opportunistic testing by health care workers at consultations unrelated to sexual health. This approach is not necessarily easier than community surveys and represents a challenge to Aboriginal communities with limited access to health resources and a different cultural perspective on sexual matters. Opportunistic testing cannot be undertaken without prior consultation with the community and the development of guidelines on who should be tested and when. The risk of acquiring an STD is not evenly distributed within Aboriginal communities and a better understanding of social and sexual networks is needed. Mechanisms will need to be in place to inform people of test results and to ensure their treatment, and that of their contacts. The provision of adequate and acceptable community-based health services that recognise the importance of STD and have the capacity and will to detect, follow up and treat cases should be a priority. This will involve the active participation of the communities concerned and is perhaps the biggest challenge facing funders and providers of health services. HIV is already present in Aboriginal communities but its extent is limited at present.6 Experience in Africa (where the main focus of successful prevention programs is the provision of quality STD health services, encouragement of early presentation and availability of effective treatment) suggests that our ability to control bacterial STD will be a major determinant in controlling the spread of HIV.7 The two reports published in this issue of the Journal2,3 suggest that we have a long way to go in controlling STD in remote communities. We have the technology to enable non-invasive testing for gonorrhoea and chlamydia. We now have to use it effectively to detect, treat and reduce the level of endemic disease. The challenge is there for public health professionals and involved communities. Russell G Waddell Clinic Manager, STD Control Branch South Australian Health Commission Fairley CK. Sexual health -- reaching out [editorial]. MJA 1997; 166: 341-342. Skov SJ, Miller P, Hateley W, et al. Urinary diagnosis of gonorrhoea and chlamydia in men in remote Aboriginal communities. MJA 1997; 166: 468-471. Mein J, Bowden FJ. A profile of inpatient STD-related pelvic inflammatory disease in the Top End of the Northern Territory of Australia. MJA 1997; 166: 464-467. Hart G. STD epidemiology in Australasia: syphilis and gonorrhoea. Venerology 1992; 5: 115-120. South Australian Health Commission 1996. Sexually transmitted diseases in South Australia. Epidemiologic report no. 9 -- 1995. Adelaide: SAHC, 1995. Feachem RGA. Valuing the past, investing in the future: evaluation of the National HIV/AIDS strategy 1993-1994 to 1995-1996. Canberra: Department of Health, Housing and Community Services, 1995. Grosskurth H, Mosha F, Todd J, et al. Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial. Lancet 1995: 346; 530-536. - To top of article - ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Russell G Waddell

Urinary diagnosis of gonorrhoea and chlamydia in men in remote Aboriginal communities Steven J Skov, Penny Miller, Wayne Hateley, Ivan B Bastian, Jenny Davis and Peter W Tait MJA 1997; 166: 468 For editorial comment see Waddell Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - ©MJA1997 Abstract Aims: (1) To evaluate the acceptability and validity of an intervention based on urine tests for diagnosis and treatment of gonorrhoea and chlamydia in men in remote Aboriginal communities. (2) To provide a prevalence estimate of these infections in the male population in the surveyed communities. Methods: First-void urine samples from 460 men in remote communities and 33 men in the Alice Springs Gaol were tested for gonorrhoea and chlamydia with at least one of polymerase chain reaction (PCR), enzyme immunoassay (EIA) and culture (gonorrhoea only). Results: One hundred and three men (20.9%) were infected with gonorrhoea or chlamydia. The prevalence of infection for gonorrhoea only was 11.7%, for chlamydia only 4.1% and for dual infection 5.1%. Eighty-eight infected men and 45 of their sexual partners were recorded as having been treated within two months of testing. PCR tests detected the largest number of infections and were the easiest to use. Conclusions: The prevalence of these infections was higher than anticipated. Urine PCR tests were acceptable to men and are well suited to the remote-community setting. As an effective alternative to urethral swabs, they permit a range of community-based strategies to address high rates of infection with gonorrhoea and chlamydia. MJA 1997; 166: 468-471 Introduction The rates of sexually transmitted diseases (STDs) in central Australia, particularly gonorrhoea and chlamydia, are among the highest in Australia and indeed the world,1,2 despite a modest decline in gonorrhoea over the past 15 years (according to notifiable diseases data from the health departments of South Australia, Western Australia and the Northern Territory). Although these infections are more common in this region than in the rest of Australia among both Aboriginal and non-Aboriginal people, most of the excess morbidity occurs among Aboriginal people (health departments' data). Many factors contribute to this situation. Dispossession, unemployment and their sequelae are the fundamental determinants of the poor health of Aboriginal people and also underlie the observed high levels of STDs. The serious under-resourcing of central Australian health services, the difficulty in maintaining confidentiality in small communities, the stigma attached to STDs, the unpleasant nature of urethral and endocervical swabs and, in particular, the frequent lack of male health care workers -- all militate against effective STD programs.3-5 Urine tests for the detection of gonorrhoea and chlamydia are now commercially available. Enzyme immunoassay (EIA) tests have sensitivities above 80% and specificities above 93%,6-9 while polymerase chain reaction (PCR) tests have reported sensitivities of 90%-100% and specificities of 98%-100%.10-14 These technologies offered exciting possibilities to address some of the difficulties in delivering STD services, so, after receiving approval from the Alice Springs Institutional Ethics Committee, the Tri-State STD/HIV Project (TSP), in collaboration with Nganampa Health Council (NHC) and the Central Australian Aboriginal Congress (CAAC), both organisations controlled by Aboriginal communities, undertook the programs described in this article. Methods The study was undertaken in four parts. Phase I: NHC provides health services to several remote Aboriginal communities and conducts annual syphilis serology screening programs in these communities. NHC maintains a population register, and all persons between the ages of 12 and 40 years who are in the communities during the screening programs are sought out and asked to participate. In April 1995, 189 men participating in this program in three communities serviced by NHC were asked to give a first-void urine sample in addition to the blood sample for the syphilis test. Phase II: In June 1995, another 218 men in the remaining three NHC communities had urine tests only; all males over the age of 12 who were present in the communities at the time were asked to participate. Phase III: In October 1995, a further 53 men were tested who had not been previously tested. Phase IV: CAAC, as part of its many functions, provides the health service to the Alice Springs Gaol. In June 1995, 33 new inmates were asked to give a first-void urine sample as part of their comprehensive health check on admission. Diagnostic tests used for gonorrhoea were culture, EIA (Abbott Gonozyme, Chicago, IL) and PCR (Roche Amplicor CT/NG, Branchburg, NJ) and for chlamydia were EIA (SYVA MicroTrak II, Palo Alto, CA) and PCR (Roche Amplicor, Branchburg, NJ) (Box 1, below). If there was insufficient urine for all tests, the order of priority was to do PCR first, then culture, chlamydia EIA and finally gonococcal EIA. To check for cross-contamination between PCR specimens, all Phase III specimens that provided sufficient urine were divided before any PCR procedures were performed. When a positive result was obtained the other half of the original sample was retested. Chocolate and/or Thayer-Martin agar plates incubated in candle jars or CO2 gaspacks were used for gonococcal culture. BioCult GC tubes (Orion Diagnostica, Espoo, Finland), which contain a modified Thayer-Martin dipslide and a CO2-generating tablet, were also trialled. Culture media were inoculated with sediment from 10 mL of centrifuged urine and incubated for up to 72 hours at 35oC on-site and/or at Western Pathology in Alice Springs. Neisseria gonorrhoeae was identified by standard methods: typical morphology of colonies, oxidase paper test, microscopy with Gram stain, and latex agglutination (Phadebact GC, Boule Diagnostics AB, Huddinge, Sweden). Urine samples for EIA and PCR were prepared on-site according to the test manufacturer's specifications and then sent to Western Pathology in Alice Springs for processing. Male Aboriginal health workers and registered nurses in each clinic were responsible for liaison with the community and collection of specimens. Each man was asked to give 25-40 mL of first-void urine in a sterile collection jar. No urethral swabs were sought. Initial preparation of urine specimens for transport to the laboratory was completed within three hours of collection. A diagnosis of infection was made and treatment was initiated if any test was positive. Resident clinic staff were responsible for offering treatment, further investigation and safe-sex education to infected men and their sexual partners. Results Study population We tested urine samples from 493 men, of whom 460 lived in six remote communities and 33 were gaol inmates. Acceptability to clients was high, with fewer than 10 men (exact count not possible) declining testing. The 460 men from remote communities represented about 60% of the male population over the age of 12 in the area serviced by the participating clinics (Box 2, below). The proportion of men tested in different communities varied from 28% to 85%. The rate of infection Based on all methods of diagnosis combined, 103 of the men tested (20.9%) were found to be infected with either gonorrhoea or chlamydia. The rate of infection in different communities varied between 14.5% and 26%. Among the gaol inmates, who originated from all parts of the southern NT, seven (21.2%) were infected. Most infections (90.3%) occurred in men aged 15-39 years and the five-year age-specific prevalence of infection in this group varied from 22% to 27% (Box 2, above). Treatment and follow-up Eighty-eight men were treated within two months of testing. The average delay between testing and treatment was 18 days. Forty-five sexual partners of infected men were also recorded as having been treated. Performance of the tests used Different combinations of tests were used in different phases. The volume of urine received from each man varied, so it was not always possible to do all the intended tests. A summary of the numbers of specimens subjected to the various tests and their relative performance is shown in Box 3 (below). During Phase II, culture for gonorrhoea using both BioCult GC tubes and standard Thayer-Martin plates was performed on 193 urine specimens. Thirteen diagnoses were made with the BioCult GC tubes and only seven were made with standard Thayer- Martin plates: all cases positive on Thayer-Martin plates were also positive on the BioCult GC tubes. During Phase III, 19 of the 20 initially positive PCR results were retested (in one case there was insufficient urine). In 18 of these cases there was complete agreement between the first and second test. One chlamydia-positive specimen was negative on the second testing. However, because of delays in transport, the tests on this specimen were done at six and eight days after collection, well in excess of the four days maximum recommended by the test manufacturers. Discussion These results highlight the need for improvements in current STD control, including surveillance programs. Based on routine clinic activity and notifications, NHC reported only 38 men with either gonorrhoea or chlamydia during the whole of 1994 (health departments' notifiable diseases data), compared with the 96 cases detected in this study. Other regions of Australia that have comparable notification rates of these infections1 may have similar problems in underdetection. The variation in participation rates in different communities and age-groups was largely attributable to the numbers of people who happened to be present at the time of the study (people in these remote communities being highly mobile), the working relationship between community members and the health staff, and the assiduousness of the health staff in conducting the program. In central Australia it is often considered, without specific evidence, that people who do not participate in such programs may be at higher risk of infection. Recent work by NHC showed no difference in rates of syphilis infection between those tested during the main body of a screening program and those tested later as part of an effort to test non-participants (Dr Penny Miller, unpublished data). The screening programs in our study were intended to identify the most effective and practical tests for everyday use in remote clinics. Collection of urethral swabs was avoided because it would not have been acceptable to the community. Hence, the study lacked a diagnostic "gold standard" and could not formally evaluate sensitivities and specificities. The published specificities of all the tests were high -- above 98% for urine PCR tests.10-14 The procedures used in Phase III demonstrated no problems with cross-contamination in PCR testing. Several studies have suggested that urine PCR tests for chlamydia are more sensitive than urethral-swab culture and highly specific.10-13 Less work has been done on urine PCR for diagnosing gonococcal infection, but two studies indicate sensitivities above 90% and specificities of 100%.13,14 In ideal conditions, the sensitivities of urethral-swab microscopy and culture are 90%-98%,15,16 but are likely to be much less in remote communities because of high staff turnover, the use of non-nutritive transport media, and frequently prolonged transport times. In such circumstances, urine PCR may be as good as or better than urethral-swab microscopy and culture for diagnosis of gonorrhoea. In any event, according to local management protocols,17 all men presenting to clinics with urethritis are offered immediate treatment for both gonorrhoea and chlamydia. In terms of practical application, PCR was superior to culture for gonorrhoea and EIA for both infections. PCR tests detected more infections with either organism than did the other tests (Box 3). Assuming that the high published specificities for the PCR tests held under field conditions, this increased rate of detection would be attributable to a superior sensitivity. The PCR test was also the easiest to use: urine is simply stored and transported at 4¡-8¡C in the same jar used to collect it. The urine must then be processed in the laboratory within four days (test manufacturer's instructions), which is usually feasible in most remote situations. In contrast, both EIA tests used require centrifuging before transport, and the SYVA MicroTrak II EIA required addition of a transport buffer. However, PCR tests do not provide information about antibiotic susceptibility. If PCR technology is to be used as the principal diagnostic tool for gonorrhoea, there would need to be accompanying sentinel systems for gonococcal culture and antibiotic susceptibility. We found that culture of first-void urine was positive in 72% of diagnoses of gonorrhoea. Sensitivities of 70%-100% for urine culture of gonorrhoea have been reported.18,19 On this basis, urine culture in addition to urine PCR for diagnosis of gonorrhoea could be performed routinely at sentinel sites and during similar programs to those reported here in order to maintain antibiotic-sensitivity surveillance. In the field situation, the BioCult GC tubes detected more gonorrhoea than standard Thayer-Martin plates and were easier and more convenient to use. The accuracy, ease of use and acceptability to men of urine PCR tests suggest several strategies to make clinical services more accessible to people, reduce the amount of disease in the community and identify individuals who are in need of safe-sex education. The use of urine tests for routine diagnosis may encourage more men to present with an STD, even if there is no male practitioner present. Health services could adopt active case-finding strategies such as opportunistic testing when people present for other reasons, including annual comprehensive health checks or community surveys. Such strategies are under consideration by health services in central Australia. For example, CAAC is seeking funding to establish an outreach program via a mobile clinic to make comprehensive well-men's check-ups, including STD checks, accessible to Aboriginal men in Alice Springs. We also examined screening as an STD control strategy. With fewer than 10 men refusing to participate, these programs resulted in 88 men who had either gonorrhoea or chlamydia and at least 45 of their sexual partners being treated. We did not have the resources to determine whether the men were symptomatic at the time of the test. However, none of them had presented to the clinic for treatment. When these findings are considered in the light of routine notifications and our own local experience, it is likely that most of these people would not have been diagnosed and treated outside these programs. Health services catering to remote Aboriginal communities in other parts of Australia may wish to consider this new technology and its usefulness in comprehensive STD education and control programs. Acknowledgements The Tri-State STD/HIV Project (TSP) is jointly funded and managed by the Commonwealth Department of Health and Family Services, Territory Health Services, the South Australian Health Commission and the Western Australian Health Department. The work would not have been possible without the support of the clinical staff of Nganampa Health Council (NHC) and the Central Australian Aboriginal Congress (CAAC). Technical advice and material resources were contributed by the TSP, NHC, CAAC, Western Pathology, Alice Springs Hospital laboratory, the Australian Army, the Northern Territory AIDS/STD Unit, Roche Diagnostics, and the Institute of Medical and Veterinary Science. John Kaldor, Russell Waddell, Frank Bowden and John Boffa all commented on earlier drafts of this paper. References National Notifiable Diseases Surveillance System. Annual report of the National Notifiable Diseases Surveillance System. Commun Dis Intell 1994; 18: 518-548 . De Schryver A, Meheus A. Epidemiology of sexually transmitted diseases: the global picture. Bull World Health Organ 1990; 68 (5): 639-654. Scrimgeour D, Rowse T. Evaluation of STD control activities in central Australia. Menzies School of Health research report. Alice Springs: Menzies School of Health, 1992. Warchivker I. Variations in health care expenditure in the Alice Springs Rural District in 1993-94. Aust N Z J Public Health 1996; 20: 11-13. McDermott R, Beaver C. Models of horizontal equity in resource allocation in Aboriginal health. Aust N Z J Public Health 1996; 20: 13-15. Roongpisuthipong A, Lewis JS, Kraus SJ, Morse SA. Gonococcal urethritis diagnosed from enzyme immunoassay of urine sediment. Sex Trans Dis 1988; 15: 192-195. Schachter J, Pang F, Parks RM, et al. Use of gonozyme on urine sediment for diagnosis of gonorrhoea in males. J Clin Microbiol 1986; 23: 124-125. Moncada J, Schachter J, Shafer MA, et al. Detection of Chlamydia trachomatis in first catch urine samples from symptomatic and asymptomatic males. Sex Trans Dis 1994; 21: 8-12. Sanders JW, Hook EW, Welsh LE, et al. Evaluation of an enzyme immunoassay for detection of Chlamydia trachomatis in urine of asymptomatic men. J Clin Microbiol 1994; 32: 24-27. Jaschek G, Gaydos CA, Welsh LE, Quinn TC. Direct detection of Chlamydia trachomatis in urine specimens from symptomatic and asymptomatic men by using a rapid polymerase chain reaction assay. J Clin Microbiol 1993; 31: 1209-1212. Bianchi A, Scieux C, Brunat N, et al. An evaluation of the polymerase chain reaction Amplicor Chlamydia trachomatis in male urine and female urogenital specimens. Sex Trans Dis 1994; 21: 196-200. Bauwens JE, Clark AM, Loeffelholz MJ, et al. Diagnosis of Chlamydia trachomatis urethritis in men by polymerase chain reaction assay of first-catch urine. J Clin Microbiol 1993; 31: 3013-3016. Mahony JB, Luinstra KE, Tyndall M, et al. Multiplex PCR for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in genitourinary specimens. J Clin Microbiol 1995; 33: 3049-3053. Komeda H, Deguchi T, Yamamoto H, et al. Detection of Neisseria gonorrhoeae in first-voided urine sediments from male urethritis patients by polymerase chain reaction. Kansenshogaku Zasshi 1992; 66: 1209-1212. Judson FN. Gonorrhoea. Med Clin North Am 1990; 74: 1353-1366. Lind I. The laboratory diagnosis of gonorrhoea. In: Facklam R, Laurell G, Lind I, editors. Recent developments in laboratory identification techniques. Amsterdam: Excerpta Medica, 1979. Central Australian Rural Practitioners' Association. The CARPA Standard Treatment Manual. 2nd ed. Alice Springs: Institute for Aboriginal Development, 1994. Woods ER, Galvez LM, Talis AL, Jean Emans S. First catch urine sediment for Chlamydia trachomatis and Neisseria gonorrhoeae in adolescent males with pyuria. J Adolesc Health 1991; 12: 329-334. Feng WC, Medeiros AA, Murray ES. Diagnosis of gonorrhoea in male patients by culture of uncentrifuged first-voided urine. JAMA 1977; 289: 896-898. (Received 24 June, accepted 17 Oct, 1996) Authors' details Tri-State STD/HIV Project, Alice Springs, NT. Steven J Skov, MPH, FAFPHM, Medical Officer, Tri-State STD/HIV Project. Nganampa Health Council, Alice Springs, NT. Penny Miller, MB BS, STD/HIV Program Coordinator. Wayne Hateley, STD/HIV Aboriginal Health Worker. Royal Darwin Hospital, NT. Ivan B Bastian, MB BS, MSc, Microbiology Registrar. Australian Army, Darwin, NT. Jenny Davis, Medical Technician. Central Australian Aboriginal Congress, Alice Springs, NT. Peter W Tait, MB BS, DipRACOG, FRACGP, Acting Senior Doctor. Reprints will not be available. Correspondence: Dr Penny Miller, Nganampa Health Council, PO Box 2232, Alice Springs, NT 0871. - To top of article - ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Steven J Skov · Penny Miller · Wayne Hateley · Ivan B Bastian · Jenny Davis · Peter W Tait