Ethics Statement

Written consent forms were gathered of all participants in this study. None of the participants asked us to be given incentives for participation in this study. The content of consent forms was approved by Ethics Committee of the Health Policy Research Center affiliated with Shiraz University of Medical Sciences and included a brief explanation about aims of this study and identifications of researchers and interviewers. The signed consent forms were kept in archive of records of this survey. According to our protocol, all potential participants who declined to participate or otherwise did not participate were eligible for treatment (if applicable) and were not disadvantaged in any other way by not participating in the study.

A 10-mL blood sample was obtained from each subject in the BCC laboratory. Blood samples were transferred promptly to the Central Blood Transfusion Organization in Shiraz with appropriate safeguards to maintain cold chain standards. Samples were tested for hepatitis B surface antigen (HBS Ag), antibody to hepatitis B core antigen (HBc Ab), antibody to hepatitis C virus (HCV Ab) and HIV. Hepatitis B e-antigen (HBe Ag) and antibody to hepatitis B e-antigen (HBe Ab) were also tested in persons who were positive for HBS Ag or HBc Ab. A third-generation enzyme linked immunosorbent assay (ELISA) was used to measure HBS Ag and HCV Ab (DIA.PRO kit, Italy). Positivity for HBc monoclonal antibody was determined by ELISA (Siemens Enzygnost, Germany). Western blot assays (MP Diagnostic HCV Blot 3.0 kit and MP Biomedicals HIV kit, Germany) were used as confirmatory diagnostic assays for HCV and HIV infection, respectively.

All data were entered into SPSS version 11.5 software (SPSS, Chicago, IL, USA). The accuracy of data entry was ensured by randomly selecting and checking completed questionnaires against their corresponding data in the SPSS software. Correlations between interval and nominal variables were determined as the Eta coefficient. Chi-square, Fisher’s exact and t tests were used as appropriate. After univariate analysis, cumulative correlations of the variables with P ≤ 0.2 (as independent variables) and HBS, HCV or HIV positivity (as dependent variables) were calculated separately for each virus by binary logistic regression (forward model). P values less than 0.05 were considered significant.

HCV

Viral hepatitis clearly poses a challenge to public health. Globally, 3–4 million people are infected with HCV every year; 150 million people are chronically infected, and more than 350,000 people die every year from HCV-related liver disease [11]. In developed countries injection drug use is the main route of HCV transmission. The hepatitis C virus is more infectious than HIV and five times more widespread worldwide [3]. There is a wide range of reported prevalences of HCV infection among IDU in different geographical regions of world. The differences in these estimates reflect uncertainties resulting from variations in prevalence among different subpopulations of IDU [7]. According to the 2012 World Drug Report, the global prevalence of HCV infection among IDU was 46.7% in 2010 [1]. However, this figure was reported as 50.3% in the 2011 World Drug Report [3]. One global systematic review showed that the prevalence of HCV infection among IDU was 60% to 80% in 26 countries and >80% in 12 countries, with a midpoint prevalence of 67% among all IDU globally [8]. The above figures show that there are 7.4 to 16 million IDU worldwide with HCV infection [1]. The largest HCV-positive IDU populations were believed to be living in Eastern Europe (2.3 million; range 1.2–3.9 million) and East and South-East Asia (2.6 million; range 1.8–3.6 million). China, (1.6 million), the USA (1.5 million) and the Russian Federation (1.3 million) had by far the largest such populations [8].

In Iran, no large changes were seen between 2008 and 2009 in the reported trend in the prevalence of HCV infection among IDU [3]. A global systematic review showed that the HCV infection rate among IDU in Iran was 50.2% (34.5% to 65.9%) in 2007 [8]. One study in Tehran, Iran reported an HCV infection rate of 34.5% in IDU compared to 40.3% in our findings [12]. In another study, the prevalence of HCV infection among drug users referred to a BCC in Hamadan province (western Iran) was 35.6% between 2005 to 2007 [13]. These prevalence figures are higher than the 19.15% found in the present study. One reason for these differences may be differences between subpopulations in different settings.

HBV

Two billion people worldwide have been infected with HBV and about 600,000 people die every year from the acute or chronic consequences of this virus [14]. According to the 2012 World Drug Report, the global prevalence of HBV infection among IDU was 14.6% in 2010 [1]. However, it was reported as 22% in the 2011 World Drug Report [3]. One global systematic review reported that in 2010, HBS Ag infection among IDU ranged from 5% to 10% in 21 countries and was over 10% in 10 countries [8]. Worldwide, 6.4 (2.3–9.7) million IDU might be anti-HBc-positive and 1.2 (0.3–2.7) million are HBs Ag-positive [8]. In low-intermediate prevalence countries, the prevalence of HBs Ag in IDU was typically <10%, whereas in high HBV prevalence countries (e.g. East and South-East Asia), the prevalence of HBs Ag among IDU was on the order of 10% to 20% [8]. The HBs Ag prevalence among IDU in Iran reportedly ranged from 3.7% to 30.9% [8]. One study in Tehran reported that 50.7% of IDU were positive for HBV infection [12], compared to 5.57% in the present study. Another report placed the prevalence of HBV infection among drug users referred to a Hamadan province BCC between 2005 to 2007 at 2.9%, a much lower figure than the 12.65% in the present study [13]. In a survey [15] conducted in 2007 at the Shiraz BCC, the prevalence of HBS seropositivity among patients with HIV infection was 7.45%, which is less than the 8.69% (2 of 23 HIV-positive participants) in the present study. The large differences between studies may be the result of heterogeneity in the subpopulations studied in different geographical areas.

HIV

Globally, the prevalence of HIV infection among IDU was estimated as 17.9% in 2009 [3] and 18.9% in 2010 [1]. According to other reports, 3 (0.8–6.2) million IDU (1 of 5 IDU) are living with HIV worldwide [1,7]. There are large geographical variations in the prevalence of HIV among IDU, with the largest numbers and highest rates in Latin America, East Europe, and East and South-East Asia. Combined, these regions account for 73% of the global number of IDU living with HIV. In some countries the prevalence of HIV among IDU is extremely high, such as in Estonia (72%), Argentina (50%) and Brazil (48%) [3]. In Iran, a decrease in the reported prevalence of HIV among IDU was seen in 2009 compared to 2008 [3]. The rate of HIV infection among IDU who participated in the present study was 7.72%, a figure lower than the 10.7% rate in another study in Tehran [12]. In an earlier study at a Hamadan province BCC [14], the prevalence of HIV infection among drug users referred to this center between 2005 and 2007 was 4%, i.e. the same as in the present study in Fars province.

HBV/HCV/HIV co-infection

The prevalence of HBV/HCV/HIV co-infection in IDU who participated in our study was 4.72%, compared to 7.1% in China [16], 6.5% in Tehran [12] and 1.3% in male IDU in a city in central Iran [17]. HBV/HCV, HCV/HIV and HBV/HIV co-infection rates in IDU in the present study were 15.02%,6.43% and 4.72% respectively, compared to 21%, 8.7%, and 7.8% in the Tehran study [12]. An earlier study at the Shiraz BCC found that 18.31% of the participants with HCV infection had also HIV infection [18]; this figure is slightly higher than the 16.51% we found in 2012 and 2013. Davarpanah et al. reported in 2004 [15] that the prevalence of HBV/HIV co-infection among persons referred to the Shiraz BCC was 7.5%, about three times the figure we found in the present study. In another study at the Shiraz BCC, the prevalence of HCV/HIV co-infection was 18.31%, more than 2.5 times the rate we detected in this study [18].

Risk factors for HBV and HCV infection

Different risk factors predispose drug users to HCV and HBV infection. Unsafe injection is one of the most common and important routes of HCV, HBV and HIV infection in IDU, and caused 46.7%, 14.6% and 18.9% respectively of infections by these viruses according to a 2010 report [1]. Unprotected sexual activity, unsafe tattooing and inappropriate cupping procedures are among other risk factors that cause these viruses to be acquired or spread in both IDU and non-IDU in the community. In one study [19] conducted at the Shiraz BCC, risk behaviors among users were injection drug use (40.8% vs 9.84% in the present study), high-risk sexual contact (16.4% vs 25.65%), and both injection drug use and unprotected sexual contact (32.6% vs 56.76%). These findings show that the proportion of high-risk sexual contacts among users of the Shiraz BCC has increased in recent years. Our study shows that around half of IDU had a history of sharing needles, a larger proportion than the 31% found in a study in Isfahan (central Iran) [20]. We also found that more than half of drug users had risky sexual contacts, two third were heterosexual, about 15% were bisexual and around 3% were homosexual, and most of them did not use a condom regularly in their sexual contacts. About half of them had tattoos, i.e. about six-fold as many as the 7.9% found in 2008 by Davarpanah et al. at the Shiraz BCC [19] and three-fold as many as Keramat et al. reported for users of a Hamadan BCC [14]. These figures show an increasing tendency toward tattooing among drug users in recent years. About 11.15% of IDU had been vaccinated for HBV compared to 33.1% of Australian IDU [21]. Therefore increasing HBV vaccine coverage in IDU should be considered. In addition, around three fourths of drug users with HBV or HCV infection (or both) had history of dental procedures before their infection was detected. This finding necessitates better knowledge of infection control and safer practices by dentists in our region. About half of drug users and especially IDU in the present study had a history of imprisonment, as was also found at a Hamadan BCC [14] and in a study in Tehran by Mir-Nasseri et al. [22]. All these lines of evidences show that most drug users, including non-IDU, have multiple risk factors. Among these high-risk groups, less educated drug users who have spent time in prison or have tattoos should be considered a high-priority population for screening and harm reduction for HBV and HCV infection, regardless of their route of drug use and regardless of whether they are HIV-positive or not.

Limitations

Our study was not free from potential limitations. We were able to study only a convenience sample of opiate users. Opiate users referred to the Shiraz BCC for harm reduction services may be more concerned about their health compared to others who are not referred to this center. We were aware of this limitation from the beginning of this study. However, this sampling method was unavoidable because many opiate users are beyond the reach of health care and social services. The same limitation applies to many published studies designed with aims similar to ours. Other limitation was that due to very high cost of molecular assays, we could not check HBV-DNA or HCV-RNA in serological positive patients, to detect those who need treatment.

In conclusion, Iran, a country with a very high rate of opiate consumption, has a large number of opiate users with HBV and HCV infection. No more than half of the estimated number of drug users are receiving care at private and public drug detoxification and harm reduction centers in Shiraz. Meanwhile only 2% of the opiate user population is referred to the BCC. Among all high-risk groups referred to the BCC, around 4% are HIV-positive and only this subgroup is tested for HBV and HCV infection. Therefore, more than 99% of opiate users remained unscreened for these viruses. This situation presents our region with a poor outlook and looming crisis regarding epidemics of HBV and HCV infection. Evidence from this study shows that the current policy of screening only HIV-positive drug users for HBV and HCV infection at the BCC in each province in Iran does not identify most of cases of these infections. Although maintaining and strengthening the response to HIV among IDU remains crucial, the significance of viral hepatitis should receive greater recognition than is currently the case. Therefore, urgent revision of the nationwide protocol should be considered by the Ministry of Health of Iran, and all opiate users should be screened for HBV and HCV infection. This need is concordant with the declaration produced by the WHO 63rd World Health Assembly in May 2010 that countries should incorporate “policies, strategies and tools recommended by WHO in order to define and implement preventive actions, diagnostic measures and the provision of assistance to the population affected by viral hepatitis” including vulnerable populations [8,23].