Volume 171 Issue 1

Abstract Objective: To investigate possible HIV transmission among prison inmates. Setting: A prison system in an Australian State. Participants: 13 ex-prisoners and their prison contacts. Methods: Ex-prisoners who claimed to have been infected with HIV in prison and their prison contacts were interviewed about HIV risk behaviour. Entries in prison and community medical records were used by a three-member expert panel to establish the likelihood of primary HIV infection and its possible timing and location. Main outcome measures: Determination of whether HIV infection probably occurred in prison. Results: There was a very high probability that at least four of 13 ex-prisoners investigated acquired HIV in prison from shared injection equipment. Another two ex-prisoners most probably acquired HIV infection outside prison. The location of infection for the remaining seven could not be determined. Conclusions: HIV transmission in prison has substantial public health implications as most drug-using prisoners soon return to the community. HIV prevention strategies known to be effective in community settings, such as methadone maintenance treatment and syringe exchange schemes, should be considered for prisoners. Introduction HIV transmission in prison has been reported in the United States,1 Scotland2 and Australia.3 The infrequency of these reports has led to a belief that HIV transmission occurs rarely among inmates. A more likely explanation is that confirmation of HIV transmission is more difficult in prisons than community settings.4 Multiple and powerful factors conducive to high HIV incidence are found in prisons. These include that: HIV prevalence is generally several times higher in prisons than in surrounding communities because of the considerable over-representation of injecting drug users (IDUs) among prisoners;5 reports of syringe sharing with multiple injectors are still common in prisons but now rare in community settings;6 HIV infection has been associated with imprisonment in France7 and Spain;8 and incidence of hepatitis C among IDUs incarcerated twice within a 12-month period was double that among IDUs who remained at liberty.9 Furthermore, HIV prevention measures, such as provision of sterile injecting equipment, condoms and methadone maintenance, are uncommon in prisons.10 Although several estimates of HIV prevalence have been conducted in correctional institutions,1,11,12 assessing the incidence of HIV transmission within a prison system poses considerably greater challenges.4 Most drug users serve short, repeated sentences. This hampers the investigation of infection outbreaks and identification of transmission location. In an earlier Australian study,13 several IDUs claimed to have become infected with HIV in prison. Some reported symptoms indicative of primary HIV infection while incarcerated. The aim of this study was to assess, using epidemiological data, whether these IDUs or their contacts had become infected in prison. A similar approach has been used to investigate an HIV outbreak in a Scottish prison.2 Methods Index cases The investigation took place between 1993 and 1994. Seven IDUs from an earlier study13 who claimed to have acquired HIV infection in prison were recontacted. In the earlier study, respondents who had injected drugs and had recently been released from prison were recruited from methadone units, hostels for ex-prisoners or drug injectors, probation offices, syringe exchange schemes, local media advertisements, AIDS organisations and via street networking.13 Prison contacts We traced prison contacts nominated by these seven people through the state methadone registry, AIDS services, drug users' organisations, HIV physicians and the State Registry of Deaths. The contacts were inmates with whom the seven index inmates had engaged in syringe sharing, anal sex or tattooing while in prison. Assessment of HIV infection HIV infection was assessed by an expert panel of three HIV physicians. The experts were provided with dates of entry to and exit from prison, HIV test results, symptoms recorded at the time the prisoner believed infection occurred, self-reported symptoms and self-reported risk behaviour. All dates were referenced in months from the year before the first detected case had last tested HIV negative. Each expert independently assessed whether the recorded symptoms indicated an HIV seroconversion illness and whether the infection occurred in prison, in the community, or if the location was indeterminate. We then accepted the majority decision in each assessment. Ethical approval Relevant ethics committees approved the study on condition that study participants' contacts in the community following their release from prison were not traced. We were also required to alert potential study participants to the possibility of legal or other consequences of admitting drug use in prison or transmitting HIV to another person. Participation in the study required signed, informed consent. Information which would identify the exact time and location of these possible infections has not been included, in accordance with requirements of one ethics committee. Results Contact tracing Between 1993 and 1994, seven male IDUs described in a previous study13 were recontacted (subjects A, B, C, D, E, F, G). They identified 20 prison contacts: six of these contacts could not be located, six had died of AIDS (according to death certificates), and two declined to participate for fear of repercussions for transmitting HIV. The six remaining contacts (H, I, J, K, L, M) plus the seven index cases made a total of 13 ex-prisoners available for investigation (Figure). Prison clusters Prison records revealed two clusters (C1, C2) of six subjects in one or two prison wings. Subjects B, E, I, K and M were held in Prison 1 (population about 250 inmates) in months 22 and 23, during which time index subject B seroconverted. Subjects B, D, I, K and M were held in Prison 2 (population about 300 inmates) in months 29 and 30, during which time contact subject K seroconverted. Index participant A was not part of either cluster, but another participant reported sharing syringes with him. Of the six deceased potential respondents, two had been part of C1 and another two had been part of C2. According to death certificates, two deceased potential respondents became infected with HIV in the year when they were held with the clusters. Cluster analysis was not possible because of the lack of records being kept on the total number of inmates held in the prison wings during the crucial times. Self-reported risk behaviour Eleven participants (A, B, C, E, I, K, M, D, F, G, L) reported syringe sharing in prison, with the first seven nominating another person in this series as a sharing partner. Contact participants I and M also reported receiving a tattoo in prison, and index subject C reported unprotected anal sex. All six deceased prison contacts wereidentified by one or more participants as having shared syringes with them around the crucial periods of months 22 and 23 and months 29 and 30. Assessment of HIV infection Medical file entries for 10 subjects (A, B, C, E, F, G, I, K, L, M) were reviewed by the expert panel. The experts concluded that five participants (A, B, C, G, K) had experienced primary HIV infection and that the most likely location of transmission for individuals A, B and C was in prison (Box 1). Overall, it was concluded that infection occurred in prison for four subjects and in the community for two (Box 2). Discussion The epidemiological evidence that individual A was infected in prison is beyond doubt: he tested negative and then positive for HIV infection after years of confinement in prison. There was strong epidemiological evidence that individuals B, C and J were also infected in prison. Individuals D and G were infected with HIV in the community. The location of infection for the remaining seven subjects (and the six deceased potential respondents) could not be determined. Thus, on epidemiological grounds, at least four of the 13 people investigated were infected with HIV while in an Australian prison system. The most likely route of HIV transmission was shared injection equipment. These are both conservative and probabilistic assessments. It is likely that a prospective investigation of these 13 people, or even a retrospective investigation closer to the events, would have yielded a larger number of confirmed HIV transmissions in prison. However, the strength of evidence for this network and the multitude of factors conducive to HIV infection in prisons suggest that the extent of HIV transmission occurring in prisons through shared injection equipment is underestimated. A mathematical model of HIV transmission in an Australian prison system14 using values derived from empirical studies also suggests that transmission is occurring within correctional centres. This study illustrates some of the difficulties of confirming HIV transmission in prison. We became aware of a possible outbreak by chance. Obtaining ethical approval for the study was an extremely protracted process requiring the assistance of a legal expert. Inmates were understandably wary of admitting risk behaviour because of the potentially serious consequences (as outlined in the consent form). Apart from the logistical and ethical problems of this type of research, the incubation period for HIV infection is almost as long as the average duration of a prison sentence served for drug-related offences in Australia. Consequently, many HIV infections occurring in prisons will not be detected by conventional surveillance. These factors may help to explain why so few cases of HIV transmission among inmates have been reported. Our study differed from previous reports10 in the extent of transmission detected and the type of prisoners studied. Previous studies have investigated long term, high security prisoners, who have less opportunity to associate with other inmates and visitors to obtain drugs and consequently become infected with HIV.15 Our study found a relatively large number of incident cases considering the small sample size, the extremely low prevalence of HIV infection in the Australian prison population16 and the rapid turnover of inmates. All these factors militate against detection of HIV transmission in prison. A limitation of the study was reliance on self-reported risk behaviour. However, we accepted self-reported data only if corroborated by another external source. Moreover, symptoms reported by informants coincided closely with medical records, supporting the validity of self-reported data. We were precluded by ethics committee requirements from determining whether any sexual partners (and their children) were infected with HIV by participants following release from prison. This restriction prevented investigation of possible HIV transmission beyond prison to the community. However, medical files indicated that four subjects had each had an HIV-positive female sexual partner following release from prison. Two of these women, and an additional HIV-negative partner, became pregnant, with at least two pregnancies reaching full term. Medical files also indicated that at the time of the investigation two former inmates had been engaging in unprotected sex with two HIV-negative women, against the advice of their counsellors. Existing evidence of HIV transmission among prisoners has persuaded prison authorities in few countries to implement effective prevention strategies for inmates. Confirmation of HIV infection from prison to the community may be more persuasive for authorities. Syringe exchange, methadone and bleach programs reduce the spread of HIV in community settings,16-18 and preliminary results from these programs in prison appear promising.19-21 The paucity of data confirming HIV transmission in prison should not be regarded as adequate justification for the lack of effective HIV prevention measures within prisons. There is already sufficient information on HIV transmission between prisoners to justify rapid implementation in correctional institutions of prevention measures shown to be effective in community settings. Improved methods of monitoring the spread of HIV within prisons and from inmates to community members following release are required urgently. Acknowledgements We are grateful to the NSW Department of Health for funding this study. We also wish to thank David Buchanan, Andrew Carr, Ying Chun Ge, David Cooper, Anthony Cunningham, Basil Donovan, John Dwyer, Tania Sorrell and Dominic Dwyer. Results of tracing 20 prison contacts of seven index cases for recruitment into the study. References Brewer TF, Vlahov D, Taylor E, et al. Transmission of HIV-1 within a statewide prison system. AIDS 1988; 2: 363-367. Taylor A, Goldberg D, Emslie J, et al. Outbreak of HIV infection in a Scottish prison. BMJ 1995; 310: 289-292. Dolan K. AIDS, drugs and risk behaviour in prison: state of the art. Int J Drug Policy 1997; 8: 5-17. Dolan K. Why is there conflicting evidence of HIV transmission in prison? In: O'Brien O, editor. Report of the 3rd European Conference on Drug and HIV/AIDS Services in Prison. London: Cranstoun Drug Services, 1997; 19-21. Gaughwin MD, Douglas RM, Wodak AD. Behind bars -- risk behaviours for HIV transmission in prisons, a review. In: Norberry J, Gerull SA, Gaughwin MD, editors. HIV/AIDS and prisons conference proceedings. Canberra: Australian Institute of Criminology, 1991; 89-107. Crofts N, Webb-Pullman J, Dolan K. An analysis of trends over time in social and behavioural factors related to the transmission of HIV among IDUs and prison inmates. Evaluation of the National HIV/AIDS Strategy. Technical Appendix 4. Canberra: AGPS, 1996. Richardson C, Ancelle-Park R, Papaevangelou G. Factors associated with HIV seropositivity in European injecting drug users. AIDS 1993; 7: 1485-1491. Granados A, Miranda MJ, Martin L. HIV seropositivity in Spanish prisons. Presented at the VIth International AIDS Conference, San Francisco. Abstract no Th. D.116, 1990. Crofts N, Stewart T, Hearne P, et al. Spread of blood-borne viruses among Australian prison entrants. BMJ 1995; 310: 285-288. Dolan K, Wodak A, Penny R. AIDS behind bars: preventing HIV spread among incarcerated drug injectors. AIDS 1995; 9: 825-832. Vlahov D, Brewer TF, Castro KG, et al. Prevalence of antibody to HIV-1 among entrants to US correctional facilities. JAMA 1991; 265: 1129-1132. Bird AG, Gore SM, Jolliffe DW, Burns SM. Anonymous HIV surveillance in Saughton Prison, Edinburgh. AIDS 1992; 6: 725-733. Dolan K, Wodak A, Hall W, et al. Risk behaviour of IDUs before, during and after imprisonment. Addict Res 1996; 4: 151-160. Dolan K, Wodak A, Hall W, Kaplan E. A mathematical model of HIV transmission in NSW prisons. Drug Alcohol Depend 1998; 50: 197-202. Dye S, Isaacs C. Intravenous drug misuse among prison inmates: implications for spread of HIV. BMJ 1991; 302: 1506. Feachem R. Valuing the past . . . investing in the future. Evaluation of the National HIV/AIDS Strategy. 1993-94 to 1995-96. Canberra: AGPS, 1996. Ward J, Mattick R, Hall W. Methadone maintenance treatment and other opioid replacement therapies. Amsterdam: Harwood Academic Publishers, 1998. Normand J, Vlahov D, Moses LE. Preventing HIV transmission: the role of sterile needles and bleach. Washington: National Academy Press, 1995. Nelles J, Harding T. Preventing HIV transmission in prison: a tale of medical disobedience and Swiss pragmatism. Lancet 1995; 346: 1507-1508. Dolan K, Wodak A, Hall W. Methadone maintenance treatment reduces heroin injection in NSW prisons. Drug Alcohol Rev 1998; 17: 153-158. Dolan K, Wodak A, Hall W. A bleach program for inmates in NSW: an HIV prevention strategy. Aust N Z J Public Health 1998; 22: 838-840. Authors' details National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW. Kate A Dolan, BSc, PhD, Research Fellow. Alcohol and Drug Services, St Vincent's Hospital, Sydney, NSW. Alex Wodak, FRACP, FAFPHM, Director. Reprints: Dr K A Dolan, Research Fellow, National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW 2052. Email: ndarc8@unsw.edu.au

Kate A Dolan · Alex Wodak

Abstract Objective: 1. To determine whether naltrexone-accelerated detoxification with minimal sedation is an acceptable and effective form of induction onto naltrexone. 2. To monitor outcomes of detoxified patients. Design: Observational study. Setting: Medical ward of a general hospital (for detoxification) and a community clinic (for follow-up) in Sydney, NSW, 1998. Patients: 15 heroin users and 15 people seeking withdrawal from methadone. Intervention: Detoxification used naltrexone (12.5 or 50 mg), with flunitrazepam (2-3 mg), clonidine (150-750 µg) and octreotide (300 µg) for symptomatic support. Patients remained awake and were discharged when they felt well enough. Follow-up was daily for four days and then weekly for up to three months for supportive care. Main outcome measures: Acute side effects; patient ratings of severity and acceptability of withdrawal; nights of hospitalisation; rates of induction onto naltrexone; retention in treatment over three months; and relapse to opioid use. Results: Acute withdrawal with delirium lasted about four hours. Octreotide was crucial for controlling vomiting; with octreotide no patient required intravenous fluids. There were no major complications. Eighteen patients (60%) reported that it was a "quite" acceptable procedure, 18 (60%) required only one night's hospitalisation, and 24 (80%) were successfully inducted onto naltrexone (defined as taking naltrexone on Day 8). Three months later, six (20%) were still taking naltrexone (with four of these occasionally using heroin) and seven (23%) were abstinent from opioids, including five not taking naltrexone. Eleven had gone onto methadone maintenance, seven had relapsed to heroin use, and one had died of a heroin overdose. Conclusions: Rates of induction onto naltrexone were comparable with those reported for accelerated detoxification under sedation, suggesting that it can be performed successfully with minimal sedation. As in other studies of naltrexone maintenance, retention was low, and relapse to heroin use was common. Introduction Since 1997, accelerated (or "rapid") detoxification has been vigorously promoted as part of a "cure" for heroin addiction. Detoxification involves providing symptomatic assistance during the acute withdrawal syndrome that occurs about 8-12 hours after last heroin use and lasts four to five days. In accelerated detoxification the process of withdrawal is speeded up with an opioid antagonist such as naltrexone,1 which precipitates a more severe but relatively brief abstinence syndrome. Private clinics in Australia have performed several hundred episodes of naltrexone-accelerated detoxification in the past 18 months. However, there has been little systematic investigation of accelerated detoxification, and existing studies are limited by variation in methods, poor research design, and lack of data on long-term outcomes.2,3 Safety is a crucial issue. Greater levels of sedation are assumed to make the procedure more tolerable, but increase the risk of aspiration.4 General anaesthesia with intubation presumably reduces this risk,2 but makes the procedure expensive. Our study was undertaken to determine whether naltrexone-accelerated detoxification can be performed with minimal sedation in awake patients. The rationale was to identify a safe, acceptable and affordable procedure for use in formal trials of accelerated detoxification as a treatment for addiction. A secondary aim was to monitor outcomes of detoxified patients treated for three months with naltrexone. Methods The study was performed in 1998 and approved by the Ethics Committee, South Eastern Sydney Area Health Service. Recruitment Enrolment criteria were either current dependence on heroin or methadone treatment for at least 12 months, and wish to transfer to naltrexone maintenance. Methadone patients were not required to be stable (abstinent from heroin) but simply to have a strong desire to discontinue methadone treatment. Exclusion criteria were serious intercurrent medical or psychiatric problems, pregnancy, and concurrent benzodiazepine or alcohol dependence. Because of publicity when the trial was announced by the New South Wales Government, no active recruitment measures were necessary. Participants were enrolled in blocks of four or six: the first four people to contact were booked for assessment, and no further bookings taken until these four had undergone detoxification. The process was repeated until 15 heroin and 15 methadone users had been enrolled. Assessment All patients were interviewed by a nurse and a doctor. Interviews lasted about an hour and covered drug use and treatment history, explanation of the proposed treatment, and exploration of patient goals and motivation. Standardised questionnaires (Severity of Dependence Scale [SDS], Severity of Opiate Withdrawal Scale, Quality of Life Inventory and System Checklist-90, a global checklist of psychological functioning) were administered. Each patient was allocated a case manager who attended detoxification and conducted follow-up. Case managers comprised a psychologist, a registered nurse and a pharmacist with counselling qualifications. Detoxification Detoxification was performed in a medical ward of a general hospital. Patients presented at 8 am, underwent a brief medical assessment (including urine pregnancy test for women), and had the procedure outlined again. Those with a history of constipation were given an enema. The approach to detoxification was primarily supportive, with repeated explanation of expected symptoms, and potential risks and benefits. Patients received oral premedication with flunitrazepam (2 mg) and clonidine (150 µg). Half an hour later, they were given oral naltrexone at a dose of 12.5 mg (first five patients) or 50 mg (subsequent patients). Oral ondansetron (4 mg) was given orally to the first four patients to control vomiting, and then intravenously when vomiting became established. However, it was observed to be ineffective and was replaced by subcutaneous octreotide (100 µg) in subsequent patients. During acute withdrawal, further clonidine (150 µg, four-hourly) and flunitrazepan (1 mg) were given if patients reported feeling agitated. Oral buscopan (200 mg, four-hourly) was given for complaints of abdominal cramps, and oral quinine sulfate (300 mg, eight-hourly) for leg cramps. Additional doses of octreotide (100 µg) were given in the evening of detoxification and the next morning. Naltrexone was given at a dose of 50 mg/day from Day 2 onwards. Patients were discharged when well enough, with instructions to continue taking this dose of naltrexone. Follow-up After discharge, patients were seen daily for four days and then weekly at a community clinic. They were encouraged to telephone between visits, and a weekly support group was available. Counselling involved feedback on their progress, wellbeing and side effects, and clarification of their objectives. They were also repeatedly warned of the risk of overdose as a result of diminished opioid tolerance while taking naltrexone. The case manager conducted research interviews on Days 35 and 91. Outcome measures During detoxification, severity of withdrawal was monitored four-hourly using the Objective and Subjective Withdrawal Scales,5 which assess signs and symptoms of withdrawal, excluding delirium. Patients were also asked to rate the severity and acceptability of withdrawal on Likert scales. Adverse reactions were monitored throughout withdrawal and over the following three months. Key outcomes were acceptability of detoxification to patients, duration of hospitalisation, success of induction onto naltrexone maintenance, retention on naltrexone, and psychoactive drug use over the ensuing three months (the latter measured with the Opiate Treatment Index6 and confirmed by urine tests). Patients were deemed to have "dropped out" of the trial if they ceased taking naltrexone for a continuous 28-day period. The last day they were known to have taken naltrexone was considered the day of attrition. Results All 30 applicants booked for assessment underwent accelerated detoxification. Their characteristics are shown in Box 1. Most had extensive histories of drug use, high levels of dependence as reflected in SDS scores, and significant social dislocation (low levels of employment and few stable relationships). Nine of the methadone patients reported heroin use in the month before detoxification. Detoxification The pattern of detoxification was predictable. The increase in initial naltrexone dose from 12.5 mg to 50 mg after the first five patients caused withdrawal to be shorter but no obvious change in severity. After premedication with flunitrazepam and clonidine, most patients became drowsy or fell into a light sleep. About 40-60 minutes after administration of naltrexone (50 mg), patients woke abruptly and began to complain of agitation and discomfort. All reported that symptoms were quite different from those of spontaneous heroin withdrawal. Symptoms escalated over the next 30 minutes, and most patients were moderately distressed. Thereafter, almost all entered a delirium for about three to four hours; they were often confused but not aggressive, none required restraint, and nursing care was straightforward. Six patients were found to have self-medicated with benzodiazepines while in hospital and were less easily managed, as higher doses of benzodiazepines appeared to increase delirium and disinhibition. After about four hours, delirium and agitation subsided. Patients felt miserable, often depressed, withdrawn and exhausted. Most had only a vague recollection of the acute phase of withdrawal. Over the ensuing 24 hours, they became increasingly alert but reported feeling "flat", "washed out" and dysphoric, and most ate little. Average dose of clonidine on Day 1 was 415 µg (range, 150-750 µg). Fourteen patients received further clonidine on Day 2. Severity of withdrawal Scores on the Objective and Subjective Withdrawal Scales did not differ significantly between the methadone and heroin groups when compared by F tests. Objective withdrawal scores peaked two hours after naltrexone administration, with a median of 5 (range, 2-9; out of a possible maximum of 13). Scores decreased within 12 hours and, at 24 hours post-naltrexone, median score was 0 (range, 0-6). Subjective withdrawal severity could not be rated during the acute phase. At 24 hours post-naltrexone, scores ranged widely, from 0-42 with a median of 23 (out of a possible maximum of 64, where 42 = quite severe). However, the primary feature of withdrawal -- delirium -- was not assessed by this scale. The first four patients who received ondansetron but not octeotride during withdrawal (three from heroin and one from methadone) all experienced repeated vomiting for more than 24 hours and required intravenous fluid replacement. All subsequent patients received octreotide. Their gastrointestinal symptoms are shown in Box 2. Vomiting was common and could occur throughout the first 48 hours, but most of those who vomited did so only once, and none required intravenous fluids. Patients withdrawing from methadone had more gastrointestinal symptoms than those withdrawing from heroin. Duration of hospitalisation varied. Among patients withdrawing from heroin, 11 needed only one night's hospitalisation, while the other four needed two nights. Patients withdrawing from methadone tended to need longer hospitalisation: seven stayed one night, five stayed two, and the other three stayed three, four and five nights, respectively. Patients who did not receive otreotide also tended to need longer hospitalisation. Patient ratings of detoxification Patient ratings of acceptability and subjective severity of the procedure are shown in Box 3. Most rated it as moderately to extremely severe, but moderately to completely acceptable. Eighteen reported that the procedure was "quite acceptable". Many volunteered that they preferred this experience to the prolonged symptoms of conventional detoxification. However, ratings were not available for five patients who had dropped out by Day 7, when they were first asked to rate their experience. Outcomes Retention (defined as continuing to take naltrexone regularly) is shown in Figure 1. One patient in the methadone group found detoxification too traumatic and was recommenced on methadone maintenance while still an in-patient. At Day 8, retention in each group was 12/15 (80%). Thereafter, attrition was progressive, with 17 people (57%) continuing to take naltrexone at Day 35, seven (23%) at Day 63, and five (17%) at Day 91. The methadone group tended to discontinue naltrexone earlier. Eight patients who discontinued naltrexone (and are therefore not included in these retention figures) underwent repeat accelerated detoxification, including two who underwent a third detoxification. Only one of these was still taking naltrexone at Day 91. Detailed outcomes after three months (Day 91) are shown in Figure 2. Although most patients discontinued naltrexone, this did not necessarily indicate relapse to opioid use. Five patients who had discontinued claimed to be abstinent from opioids (defined as a continuous 28-day period free of opioid use). This was confirmed by serial urine tests in four patients. The other moved interstate within a week of detoxification and did not have urine tests, but reported being drug-free during follow-up telephone interviews. Continuing to take naltrexone was not always associated with abstinence from opioids. Of the six patients still taking naltrexone at three months, four reported sporadically omitting one or two doses, using heroin, and then resuming naltrexone. However, their level of heroin use was clearly less than before detoxification. Another patient from the heroin group who continued taking naltrexone remained abstinent from heroin but took up cannabis smoking. Cannabis use increased from nil before detoxification to 10 "cones" per day at three months. There was no increase in self-reported use of non-opioid drugs among other patients. The patient who died had discontinued naltrexone use after five weeks. Three weeks after last attending the clinic and receiving a week's supply of naltrexone, this patient died of a heroin overdose. Two other patients who relapsed to heroin use reported overdosing and being revived with naloxone after misjudging their level of tolerance. Discussion We found that heavy sedation was not necessary for effective accelerated detoxification. Of 30 patients who underwent naltrexone-accelerated detoxification with only light sedation, 18 (60%) reported that it was "quite" acceptable, and 24 (80%) were successfully inducted onto naltrexone. However, attrition was high; three months later only six patients (20%) were still taking naltrexone (four of whom occasionally used heroin), and only seven (23%) were abstinent from opioids. Recent literature on opioid withdrawal has focused on controlling withdrawal symptoms with medications, at the expense of psychological treatment.7 However, use of multiple medications, including sedatives and anaesthetics, increases the risk.8 For example, a recent Spanish study of accelerated detoxification performed under sedation in an intensive care unit reported a complication rate of 4.3%, with six of 300 patients requiring intubation, and one developing aspiration pneumonia.4 In contrast, no acute life-threatening complications occurred in our study, but it was too small to establish safety definitively. The main risk we identified was self-medication with benzodiazepines, which led to greater agitation and disinhibition. Although the procedure was performed with no problems in a hospital ward, it could not be performed safely without close professional supervision. Our technique of detoxification was "ultra-rapid" -- acute detoxification was complete within hours. The acute phase was not as difficult for patients as the 48 hours post-detoxification, when they experienced gastrointestinal distress and feelings of exhaustion. Withdrawal from methadone appeared more severe, with more gastrointestinal side effects, higher ratings of severity, and longer inpatient stays. There are few published, systematic studies of withdrawal under sedation for comparison with our study. After detoxification under anaesthesia, symptoms can occasionally be severe,9 and a recent study reported that significant withdrawal symptoms persisted at least a week later.10 Our rate of induction onto naltrexone (80%) was comparable with rates reported by most others for accelerated detoxification. The only randomised trial to date to compare accelerated and conventional detoxification found rates of induction (defined as taking naltrexone at Day 8) of 65% after clonidine alone, 60% after buprenorphine, and 54% after combined naltrexone-clonidine.11 These differences were not statistically significant. In our study, hospitalisation for at least one night was probably crucial to our higher rate of induction onto naltrexone. Most studies of naltrexone maintenance have shown high dropout rates and high relapse rates to heroin use,12 similar to our findings. For example, a recent review calculated that, for people who took a first dose of naltrexone after conventional induction, average reported attrition was 39% in the first two weeks.13 Although claims have been made that mean retention on naltrexone is one to six months, depending on patient selection and quality of adjunctive services,14 this value is skewed by the small proportion of patients who take naltrexone long term, for whom the treatment is highly successful. In our study, which involved unselected patients with poor prognostic indicators, retention (defined as continuing to take naltrexone) was 58% at one month, 23% at two months, and 17% at three months (or 20% including the patient who resumed naltrexone use after repeat detoxification). Most of those who relapsed entered methadone treatment. A report on 781 heroin users in Western Australia estimated that 87% of those who underwent detoxification continued with naltrexone, with subsequent retention rates of 60% at one month, 44% at two months and 33% at three months.15 However, as these figures were based on monthly prescriptions dispensed, they may slightly overestimate retention. Another Australian study of naltrexone reported that only two of 43 patients (5%) took naltrexone for six months.16 Some studies have reported much higher rates of heroin abstinence after naltrexone treatment than ours. For example, a recent study of patients undergoing accelerated detoxification under anaesthesia reported 60% of patients were free of heroin use six months later.9 However, this was based on a telephone survey of patients who could be contacted, and would require confirmation in more rigorous trials. A Spanish study reported that 93% of 300 patients were abstinent from opioids a month after accelerated detoxification under sedation (confirmed by urine testing).4 This is in stark contrast with most previous results.12,13 Naltrexone maintenance carries risk, with a report of suicides and fatal overdoses.17 In our study, despite repeated warnings about diminished opioid tolerance when taking naltrexone, one patient died of a heroin overdose and two others reported overdosing after misjudging their tolerance. Others may have had similar experiences but not reported them. This problem needs special monitoring, as post-naltrexone deaths may be hard to identify; naltrexone is almost never found at postmortem toxicological analysis as overdose occurs when the drug is stopped. Therefore, any major study of naltrexone risk needs to monitor death records. From our data, accelerated detoxification with light sedation resulted in induction and retention rates similar to those found in most published studies of naltrexone. Randomised trials are required to compare techniques of detoxification, and our study has identified a low-cost, low-risk approach for use in such trials. However, results will not be available for years. In the meantime, as uptake of accelerated detoxification has far outstripped research, results of this pilot study may help consumers and health professionals judge the claims made for naltrexone treatment. Acknowledgements This study was funded by NSW Health. References Riordan CE, Kleber HD. Rapid opiate detoxification with clonidine and naltrexone. Lancet 1980; 5: 1079-1080. O'Connor PG, Kosten TR. Rapid and ultrarapid opioid detoxification techniques. JAMA 1998; 279: 229-234. Kleber HD. Ultra-rapid opiate detoxification. Addiction 1998; 92: 1929-1933. Seoane A, Carrasco G, Cabre L, et al. Efficacy and safety of two new methods of rapid intravenous detoxification in heroin addicts previously treated without success. Br J Psych 1997; 171: 340-345. Handelsman L, Cochrane KJ, Aronson MJ, et al. Two new rating scales for opiate withdrawal. Am J Drug Alcohol Abuse 1987; 13: 293-308. Darke S, Hall W, Heather N, et al. Development and validation of a multidimensional instrument for assessing outcome of treatment among opioid users: the opiate treatment index. Br J Addict 1992; 87: 593-602. Mattick RP, Hall W. Are detoxification programmes effective? Lancet 1996; 347: 97-100. Mayor S. Specialists criticise treatment for heroin addiction. BMJ 1997; 314: 1365. Rabinowitz J, Cohen H, Tarrasch R, Kotler M. Compliance to naltrexone after ultra-rapid opiate detoxification. Drug Alcohol Depend 1997; 47: 77-86. Scherbaum N, Klein S, Kaube H, et al. Alternative strategies of opiate detoxification: evaluation of the so-called ultra-rapid detoxification. Pharmacopsychiatry 1998; 31: 205-209. O'Connor PG, Carroll KM, Shi JM, et al. Three methods of opioid detoxification in a primary care setting: a randomized trial. Ann Intern Med 1997; 127: 526-530. Jaffe J. Pharmacological treatment of opioid dependence: Current techniques and new findings. Psychiatric Annals 1995; 25: 369-375. Tucker T, Ritter A. Naltrexone: a literature review. Melbourne: Turning Point Alcohol and Drug Centre, 1998. Kleber HD. Naltrexone. J Substance Abuse Treatment 1985; 2: 117-122. Australian Medical Procedures Research Foundation. Perth Naltrexone Trial report. Perth: AMPRF, 1999. Foy A, Sadler C, Taylor A. An open trial of naltrexone for opiate dependence. Drug Alcohol Rev 1998; 17: 167-174. Miotto K, McCann MJ, Rawson RA, et al. Overdose, suicide attempts and death among a cohort of naltrexone-treated opioid addicts. Drug Alcohol Depend 1997; 45: 131-134. Authors' details The Langton Centre, Sydney, NSW. James R Bell, BA, FRACP, Director; Malcolm R Young, RN, Registered Nurse; Sibyl C Masterman, MA(Psych), Psychologist; Amanda Morris, B Pharm, Pharmacist. National Drug and Alcohol Research Centre, Sydney, NSW. Richard P Mattick, PhD, Director of Research. National Centre for Epidemiology and Population Health, Australian National University, ACT. Gabriele Bammer, PhD, Senior Fellow.

James R Bell · Malcolm R Young · Sibyl C Masterman · Amanda Morris · Richard P Mattick

Transmission of hepatitis C within Australian prisons Transmission of hepatitis C virus (HCV) within prisons has long been suspected but has not been satisfactorily documented. We present four cases of HCV infection occurring during periods of continuous imprisonment. Each subject was HCV seronegative on entering prison and on repeat testing after 4-52 months in prison, but subsequently became seropositive. Two subjects gave a history of injecting drug use, and the most likely means of infection in the other two subjects were lacerations from barbers shears and lacerations arising from physical assault. There is an urgent need for detailed study of the incidence of HCV infection and the modes of transmission in prisons. Introduction The prevalence of hepatitis C (HCV) infection in voluntary screening among entrants to Australian and North American prisons is as high as 40%.1-3 It is therefore surprising that HCV transmission within prisons has not been well documented, although it is known that a history of incarceration is an independent risk factor for HCV seroconversion4 and uninfected prisoners are at high risk of seroconversion by the time of a second prison entry.1,3 These observations provide only indirect evidence of transmission within prisons, as infection could have occurred either during the first period of imprisonment or outside prison between release and re-incarceration. This report describes the first published series of well-documented cases of transmission of HCV within a prison. The Research Ethics Committee of the Corrections Health Service of New South Wales approved reporting of these cases. Clinical records Between April 1994 and October 1997, four male prisoners presented with HCV infection appearing a minimum of 11 months after entry to prison (Table). All had had negative HCV antibody tests on entry to prison and again after 4-52 months of continuous incarceration (anti-HCV ELISA version III, Murex Diagnostics, Kyalamani, South Africa; confirmation by Innotest HCV Ab III assay, Innogenetics, Zwijnaarde, Belgium). All bore tattoos, but all four stated that no tattoos had been applied within two years of the last negative HCV antibody test. None had received blood products, or undergone medical or dental procedures, including vaccination, in the year before acquisition of HCV. All four denied any body piercings within two years of the last negative HCV antibody test, or sexual intercourse with another person since entering prison. Case 1 A 23-year-old inmate requested an HCV antibody test after receiving a scalp laceration during a close-shave haircut (performed with electric shears without a plastic guard) in June 1997. There was minimal bleeding and the wound did not require suturing. The patient denied having injected drugs at any time, but admitted to smoking marijuana and snorting cocaine in the past. Indeed, he regarded any injection with abhorrence and feared bloodborne infection. As a result, he had requested HCV antibody tests after numerous low risk events in prison and was repeatedly seronegative. After this latest incident, the patient again requested serological tests for HCV, and seroconversion was documented six weeks later. The patient stated that several of the four preceding inmates on whom the barbers shears were used on the same day were HCV antibody positive and had also received minor lacerations during their haircuts. He also claimed that the electric shears were not disinfected in any way between uses. No further details are available of the barber's list for that day, as no permanent records of these lists are kept. Sterilisation of shears before reuse was not normal practice at the time. One of the other inmates on whom the shears were used was confirmed to be positive for HCV antibody and HCV-RNA by polymerase chain reaction (PCR) analysis (Amplicor HCV detection kit, Roche Diagnostic Systems, Branchburg, NJ, USA). Case 2 A 35-year-old inmate suffering from lassitude and anorexia presented for examination. He had started using intravenous drugs for the first time after being in prison for several years. For a period of six months, he had injected two to three times per week, frequently sharing needles with known HCV-seropositive inmates, but routinely sterilising the injecting apparatus using a recommended bleaching protocol with 5.25% hypochlorite solution.4 Six weeks after ending drug use, he developed the symptoms described, which, in association with raised alanine aminotransferase (ALT) levels, were consistent with viral hepatitis. HCV seroconversion was found to have taken place since his last negative test one year previously. Case 3 A 27-year-old inmate presenting with lassitude was found to have abnormal liver function tests typical of acute viral hepatitis. The patient was an infrequent injecting drug user who had continued his habit intermittently during imprisonment. As he was aware of the risk of transmission of bloodborne pathogens, he used a bleached injecting apparatus for each episode, but shared the mixing spoon in which the drug suspension was prepared. HCV seroconversion was confirmed. Case 4 A 25-year-old inmate presented for examination after being involved in a physical assault with another inmate, during which blood-to-blood contact occurred from abrasions and lacerations. He had sustained no serious injury. The other inmate was a known HCV-positive injecting drug user who later left prison and was lost to follow-up. Blood taken soon after the assault was negative for HCV antibodies, but seroconversion, associated with mild symptoms of hepatitis, was documented three months later. The patient denied injecting drug use. Discussion These cases provide strong evidence that transmission of HCV occurs in prison. Infection during injecting drug use is likely to be a leading mode of HCV transmission in prisoners. Inmates report that injecting apparatus is scarce in the prison system, whereas heroin is readily obtained. These circumstances favour repeated use of a limited number of needles and syringes by many prisoners. The recommended bleach cleansing of the injecting equipment appears ineffective, as our report corroborates previously documented transmission of HCV, but not HIV, after sharing of cleaned injecting apparatus.5 In two of the cases, HCV may have been transmitted by means unrelated to injecting drug use. The high prevalence of HCV among those entering prison, together with the strong likelihood of blood-to-blood contact in the prison environment, may increase the chance of HCV transmission by barbers shears, during physical assault or by other mechanisms.6 However, a limitation of our study is the reliance on self-reporting of risk factors by prison inmates. Inmates' self-reporting is relatively accurate if their status is unlikely to be affected by the content of the report, but may be biased if they perceive that harm or benefit may result.7 Our study provides the strongest evidence to date that transmission of HCV infection occurs within prisons. Two cases of HCV seroconversion among prisoners in Maryland (USA) have been reported:2 of 164 prisoners who tested negative for HCV on entry to prison, two tested positive 18 months later. However, there was not unequivocal evidence that HCV transmission occurred within prison, as the initial negative HCV test may have been carried out during the window phase between infection and seroconversion if viral transmission occurred outside prison shortly before incarceration. In our study, all four subjects were seronegative for HCV after 4-52 months' continuous imprisonment, and remained in continuous full-time custody until seroconversion was documented (Table). Approximately 10 500 imprisonments occur annually in New South Wales, which has a population of 6 300 000. At any one time, the NSW prison population is about 6000. The average sentence is seven months, and there are more than 25 000 transfers between prisons each year. Thus, the prison population has a high turnover and is not isolated from the general community. The extent of HCV transmission may be significant because of the prevalence of high-risk behaviours in prison, and the fact that some harm-reduction measures, such as needle exchange programs, are not available in Australian prisons. Thus, the prison community is a population at significant risk of HCV infection and a potentially important source of subsequent transmission of HCV into the general community. The cases presented here probably represent only a small fraction of inmates acquiring new HCV infection in prison. Firstly, our cases were detected clinically (whereas most primary HCV infections are subclinical) and, secondly, our study did not attempt a systematic search for HCV transmission among inmates. Moreover, there are rare occurrences of HCV infection without detectable HCV antibodies, and such cases depend on HCV-PCR testing for diagnosis.8 This report confirms that HCV is currently being transmitted within NSW prisons. The circumstances for acquisition of serious bloodborne infections during imprisonment should be identified and opportunities for transmission minimised where possible. Accordingly, detailed studies of the incidence of and risk factors for HCV transmission within prisons are urgently needed, followed by development and implementation of control measures. References Crofts N, Stewart T, Hearne P, et al. Spread of bloodborne viruses among Australian prison entrants. BMJ 1995; 310: 285-288. Vlahov D, Nelson KE, Quinn TC, Kendig N. Prevalence and incidence of hepatitis C infection among male prison inmates in Maryland. Eur J Epidemiol 1993; 9: 566-569. Butler TG, Dolan KA, Ferson MJ, et al. Hepatitis B and C in New South Wales prisons: prevalence and risk factors. Med J Aust 1997; 166: 127-130. van Beek I, Dwyer R, Dore GJ, et al. Infection with HIV and hepatitis C virus among injecting drug users in a prevention setting: retrospective cohort study. BMJ 1998, 317: 433-437. Bodsworth NJ, Robertson M, Kaldor J. Transmission of hepatitis C but not human immunodeficiency virus type 1 following sharing of injecting equipment. Genitourin Med 1994; 70: 206-207. Gill ON, Noone A, Heptonstall J. Imprisonment, injecting drug use, and bloodborne viruses: a threat of transmission but an opportunity for prevention. BMJ 1995; 310: 275-276. Darke S. Self-report among injecting drug users: a review. Drug Alcohol Depend 1998; 51: 253-263. Gretch DR. Diagnostic tests for hepatitis C. Hepatology 1997; 26 Suppl 1: 43S-47S. Authors' details Drug and Alcohol Services, Royal Prince Alfred Hospital, Sydney, NSW. Paul S Haber, MD, FRACP, Staff Specialist. Public Health Nursing Unit, Corrections Health Service, Sydney, NSW. Sandra J Parsons, RN, Clinical Nurse Consultant; Susan E Harper, RN, Public Health Nurse. Virology Division, Department of Microbiology, South Eastern Sydney Area Laboratory Services, Sydney, NSW. William D Rawlinson, PhD, FRACP, FRCPA, Division Head. Peter A White, PhD, Research Fellow. School of Pathology, University of New South Wales, Sydney, NSW. Andrew R Lloyd, MD, FRACP, Associate Professor, Inflammation Research Unit.

Paul S Haber · Sandra J Parsons · Susan E Harper · Peter A White · William D Rawlinson · Andrew R Lloyd