1 Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
2 Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
3 Guangxi Centers for Disease Control and Prevention, Guangxi Province, China
4 Center for Urban Epidemiological Studies, New York Academy of Medicine, New York, New York, USA
Correspondence: Xiao-Fang Yu, Associate Professor MMI, JHBSPH E5148, Baltimore, MD 21205, USA. Email: xfyu{at}jhsph.edu
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Abstract |
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Methods A longitudinal cohort of young injection drug users (IDU) from southern China was established to study the risk factors for blood-borne infections (597 subjects). Individuals underwent analysis for the presence of hepatitis B surface antigen and antibodies to human immunodeficiency virus type 1 (HIV-1), HCV and hepatitis B surface antigen. Using self-reported risk behaviours, multivariate regression analysis was performed for factors associated with HCV prevalence and seroconversion.
Results At baseline, HIV-1 and HCV prevalence was 17% and 72%, respectively. Significant factors associated with HCV seroprevalence included age >25 years (odds ratio [OR] = 1.71) and injection drug use for >2 years (OR = 2.60). HCV prevalence within one year of starting heroin use was 57% for any route of administration, and 80% if restricted to injectors. After two 6-month follow-up visits, 56 out of 159 baseline HCV seronegative individuals (148.9 total person years [py]), underwent seroconversion at an incidence rate of 37.6 per 100 py. Individuals who reported injection drug use were more likely to undergo HCV seroconversion (rate ratio [RR] = 6.59).
Conclusions HCV infection is rapidly acquired in heroin users who adopt injection in southern China. This study emphasizes the urgent need to implement and expand injection prevention and primary substance abuse prevention programmes in China.
Accepted 20 August 2003
The World Health Organization estimates 3% of the world's population is infected with Hepatitis C Virus (HCV).1 HCV is efficiently transmitted through injection drug use. The prevalence of HCV in injection drug user (IDU) cohorts in the US has ranged between 27% and 90%.27 Incidence rates of HCV within IDU cohorts have ranged from 10 to 37.3 per 100 person years (py).2,4,711 Risk factors for HCV seroprevalence have included older age, longer length and higher frequency of drug injection, and direct and indirect needle sharing.2,5,12,13
Studying the dynamics of HCV transmission within IDU cohorts has revealed potential time points for mobilizing prevention strategies. Within the Baltimore ALIVE cohort3 HCV prevalence quickly reached 80% within 2 years of injection drug use. Conversely, IDU cohorts in Chicago,12 ****San Francisco5 and New York City6 observed a more gradual incline in HCV prevalence by duration of injection drug use. HCV prevalence, population demographics, and risk behaviours may be behind the different observed HCV dynamics. Unfortunately, few data exist on HCV incidence in areas of explosive growth of injection drug use that are now occurring in developing countries and countries with newly relaxed border restrictions and increased trade such as Russia and China.
The WHO has estimated that 2.54.9% of China's population is HCV positive.14 With an estimated population of 1.2 billion people, the number of HCV infected individuals in China could exceed 50 million. In 2000, the Chinese government reported that there are approximately 800 000 documented drug users in China, while the actual number could be many times higher (Chinese Ministry of Health, 2000). Although China has a long history of opiate abuse, injection as a route of administration of heroin did not emerge until the late 1980s when the southern borders were opened and trade increased with the West.15 Consequently, the emergence and spread of human immunodeficiency virus type 1 (HIV-1) and HCV through southern China has followed drug trafficking routes from the Golden Triangle region of heroin production in SE Asia.16
Studies of injecting heroin users in southern China found newer and younger heroin users quickly switched from smoking to injection drug use.17 Since the majority of individuals who contract HCV will develop persistent infection, IDU become a reservoir for transmission to other users and the non-using community.18 The aims of this study were to longitudinally follow heroin users to estimate HCV incidence and risk factors for acquisition and spread of HCV to better target prevention strategies.
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Materials and Methods |
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Data collection
The informed consent procedure has been described previously.20 Briefly, at each visit, participants underwent a physical examination, venipuncture, and interview about health, drug, and sex risk behaviours. IDU were defined as people with any history of injection drug use in their lifetime. Other drug risk questions included the method and frequency of drug use, and the length of both total drug use and time since first injection. Questions relating to needle use included whether they reused needles, if and how they cleaned needles between uses, and whether and how often they shared needles with other IDU. A sexually active individual was defined as a person that has ever had sex. After each visit, participants were counselled on the results of their serological tests. Study participants receive 80 Chinese Yuan ($10.00) for each follow-up visit to compensate for travel, time, and a meal. The protocol was reviewed and approved by the Johns Hopkins Bloomberg School of Public Health institutional review board.
Serological assays
At the Guangxi Center for Disease Control and Prevention in Nanning, the presence of HIV-1 antibody was determined by enzyme-linked immunosorbant assay (ELISA) using the Vironostika HIV-1 Microelisa System (Organon Teknika). All ELISA-positive samples were not considered HIV-positive until confirmation by HIV-1/2 Western blot immune assay manufactured by Gene Lab (Singapore). Hepatitis B surface antigen (HBsAg) and antibody to Hepatitis B surface antigen (HBsAb) were screened using an HBV ELISA (Xiamen Xinchung Scientific, Xiamen, China). HCV antibody was detected using the Ortho HCV Version 3.0 ELISA Test System (Ortho Diagnostic Systems, Raritan, NJ). Each sample was run in duplicate and positive samples were determined by the manufacturer cutoff value (average of 3 negative samples + 0.600). Since this is a longitudinal study, we have multiple visits after HCV seroconversion. All individuals who seroconverted to HCV remained HCV EIA positive at all follow-up visits.
Data analysis
Categorical variables were analysed with the use of the 2 test. Logistic regression analysis was performed to identify factors affecting HCV seropositivity. Univariate logistic analysis was first used to explore crude associations. Variables that were significant in the univariate model (P < 0.1) were shown and then put into a multiple logistic regression model.21 Those that ceased to be significant in the multivariate model were eliminated in a stage-wise manner, yielding a final model in which all variables were independently associated with HCV seropositivity. Median values in continuous variables were used as cutpoints. P-values reported are two-sided. Incidence data were calculated using person-time techniques, and multivariate adjustment was performed using Poisson regression methods. Right censoring method was used in the estimation of incidence rate. Although exposure variables were obtained by self reporting which may be subject to a variety of distortions, literature on the validity of self reports among injection drug users is extensive and concludes that self reports are reasonably accurate in settings where responses are not tied to sanctions.22
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Results |
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When asked how many times they reused the same needle, 48% reported using needles more than once. Of those who reused needles, only half said they cleaned the needle between uses. When asked how they cleaned needles between uses, 74% rinsed only with water, 18% boiled the needles in water, and about 6% cleaned them with alcohol. Over 50% answered that they share needles and of those that shared needles, 11% shared everyday. When asked why they shared needles, over half said they shared due to the difficulty of accessing needles. The remaining individuals said they shared needles due to the ease in sharing the drug once the powdered heroin had been dissolved and the better high achieved while sharing with local friends.
At baseline 17.3% were HIV-1 positive, 72.0% were HCV positive, 44.4% were HBsAb positive, and 15.4% were HBsAg positive (Table 1). In addition, 98% of HIV-1 positive individuals were also HCV positive at baseline. The prevalences of HIV-1, HCV, and hepatitis B virus were examined by duration of any heroin use (Figure 1) and injection heroin use (Figure 2). In individuals with less than one year of any heroin use, HCV prevalence was over 55% and increased to over 80% in individuals who had used heroin for >5 years (Figure 1). HIV prevalence remained steady near 10% until individuals had used heroin for >3 years when it climbed and remained at 20%. By duration of injection heroin use, HCV prevalence was already over 70% in individuals with one year of injection drug use and reached a prevalence of over 90% in individuals with 4 years of injection drug use experience (Figure 2). HIV-1 had a gradual incline in prevalence by duration of injection drug use, reaching 30% prevalence in individuals with 5 years of injection drug use. Markers for hepatitis B remained relatively steady at 60%.
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Discussion |
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Analysing HCV seroprevalence by duration of injection drug use suggested that within one year of adopting injection drug use, HCV prevalence exceeded 70% and continued to climb reaching over 90% within 4 years. The prevalence of HIV-1 in our cohort gradually increased with time with an incidence rate similar to other injection cohorts.3,7,8 The overall seroprevalence for HBsAg and HBsAb remained relatively constant. High HCV prevalence among IDU of short duration could reflect rapid transmission or inaccurate self reports. However, the low prevalence of hepatitis B virus and HIV among IDU of short duration provides evidence more for the former than the latter. One report of similar high HCV prevalence after a short duration of injection drug use was in the ALIVE cohort in Baltimore.3 Other IDU cohorts have described a more gradual increase in HCV prevalence, reaching over 60% only after >6 years of injection drug use.2,3,5,6
In our cohort young, new heroin users are quickly adopting the injection route of administration and becoming infected with HCV.17 At baseline, individuals who did not report injection drug use had a 28.3% seroprevalence of HCV (n = 30). It is possible that risk factors other than injection drug use might have been responsible for HCV transmission in these individuals. Current literature on non-injection drug users (NIDU) reports HCV prevalence ranging from 10% to 35%.2325 Possible routes of HCV infection in NIDU include sexual transmission, tattooing, and sharing of drug paraphernalia.26 Unfortunately, analysis of factors for HCV seroprevalence failed to result in any significant associations with factors included in our questionnaire (data not shown). Further studies of HCV in the NIDU population are therefore needed.
Alternatively, since injection drug use was determined by self-reporting, underreporting of injection drug use is possible. We examined the NIDU who were HCV positive at baseline (n = 30) and found that 22 reported injection drug use at follow-up visits. We speculate that some participants may have had insufficient rapport with this study to acknowledge drug use at baseline, but with emerging comfort with the study, reported a history of injection at the follow-up visit. Thus, while we cannot exclude other possible routes of infection, we consider this explanation the most plausible given the literature on HCV transmission.
Since the dynamics of HCV infection rely on the size of the susceptible population and probability of contact with infectious individuals, the risk behaviour of the susceptible population becomes important. In cohorts with high HCV seroprevalence (>65%), HCV incidence was much lower (<13 per 100 py) and likely due to decreases in injection drug use and fewer high risk behaviours in the susceptible population.7,27 The majority of our susceptible population were young, new injection drug users with high risk behaviours. Furthermore our HCV prevalent population was shown to have high levels (>91%) of HCV RNA (data not shown). The high level of HCV RNA positive infectious individuals and high risk behaviours in our susceptible population are likely responsible for our continued high rates of HCV seroconversion. Our recruitment strategies may have resulted in enrolling many local networks of IDU. Therefore, this convenience sample may introduce bias into our results. Whether these networks are accurate reflections of HCV transmission and what factors are responsible for the extremely high rate of HCV transmission in our cohort are currently being investigated.
In this study we found sexual activity actively linked with HCV seroincidence. Current literature on the very low rate of HCV sexual transmission makes this transmission route very unlikely in our cohort.2830 It is possible sexual activity represents a marker for other high risk factors such as sharing other injection paraphernalia like cookers, filters or rinsing water, or sharing drugs by front loading.2,13 More investigation into these risk factors is currently underway. Additionally, we can confirm that the individuals in our cohort are not professional blood/plasma donors and have not received blood transfusions. Seroprevalence of HCV in the non-drug using population in China is estimated to be less than 5%, although most studies for HCV have been performed in northern China and in large cities.31
In conclusion, the adoption of the injection route of heroin use in China is responsible for the rapid acquisition of HCV and spread of HIV-1. While traditional infection prevention programmes that include education, testing, counselling, drug abuse treatment, and expanded access to sterile syringes are needed, the rapid acquisition of HCV infection among young, newly initiated injectors highlights the need to promote programmes to reduce transition from oral to injection drug use and for primary substance abuse prevention.32
KEY MESSAGES
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Acknowledgments |
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References |
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