Almost all epidemiological studies have shown that the hepatitis C virus (HCV) is primarily a blood-borne or parenterally transmitted infection. The most efficient mode of hepatitis C transmission is through percutaneous exposure such as occurs during needle-sharing, transfusion of contaminated blood and blood products, hemodialysis, reuse of contaminated instruments for medical or personal care (including tattooing devices, acupuncture needles, razors, and manicure tools) and organ transplants [1,2]. These practices have led to the rapid and global dissemination of HCV [3-5].
During the 1970s and 1980s, the most important source of HCV infection in developed countries was transmission via exposure to contaminated blood or blood products [6,7]. Once the blood supply could be effectively screened for HCV, the most important risk factor for the transmission of HCV in developed countries became the sharing of needles and other implements for illicit intravenous drug use, which now accounts for up to 60% of infections [8-11]. Although the risk of HCV transmission via blood transfusion was significantly reduced following the introduction of an anti-HCV testing in the early 1990s [12], a worldwide increase in the prevalence of hepatitis C virus infection could still occur due to the unsafe, unnecessary and yet routine injections in outpatient clinics in developing countries; this type of transmission would account for most of the "sporadic" cases [13-15].
In 2007, the global portrait of HCV is still incomplete because many countries have not defined the relative contribution of the various modes of infection with population-based studies. In these countries, the role of each risk factor in the transmission of HCV still needs to be determined or at least estimated [16-19].
TRANSFUSIONS
Prior to the introduction of routine screening of blood and blood products in the early 1990s, the transmission of HCV through contaminated blood or blood products accounted for over 85% of post-transfusion hepatitis cases [6,20].The risk of infection following transfusion of 1 unit of HCVcontaminated blood was estimated to be greater than 90% [21], and the risk of infection associated with transfusion was nearly 20% per unit transfused in the United States [22]. Following the introduction of routine testing of donated blood and restrictive criteria for blood donor selection, HCV infection through blood transfusion has been virtually eliminated in developed countries. The use of viral inactivation processes in the manufacture of blood products has eliminated transmission of HCV via clotting factor concentrate and other blood products [23]. Posttransfusion hepatitis C levels are now as low as 0.03%-0.0004% per unit transfused [24]. Nevertheless, sporadic cases of transfusion-transmitted infections still occur [25] because recently infected donors fall into the serological window period, and are therefore responsible for a lowlevel risk of hepatitis C transmission in transfusion [24,26,27]. Even though the widespread implementation of HCV nucleic acid testing (NAT) in some countries has further decreased the residual risk of acquiring hepatitis C through blood transfusions, the overall contribution of HCVNAT towards reducing the risk of transfusion transmitted hepatitis is marginal, and unfortunately less effective than previously expected in most countries. It is clear that the identification of a few window period donations per year will have a minimal effect on the overall burden of liver disease [28]. Despite this evidence it is unlikely that HCV-NAT will be discontinued because the legal interpretation of the "better safe than sorry'' precautionary principle implies that governments must adopt all possible measures to increase blood safety, regardless of the nature of the risk; any failure to do so would leave them at fault and liable for damages [29].
The portrait of blood transfusion is very different in many developing countries, where blood transfusions remain a major cause behind the spread of HCV.There are enormous disparities between countries with regard to blood transfusion safety, largely related to their level of socio-economic development. In 2001-2002, it is estimated that more than 6 million blood units were not screened for major blood-borne infections, including HCV [30]. National regulatory authorities should ensure that only blood products of demonstrated quality, safety and efficacy are used [9]. The reduction and elimination of HCV transmission through the global introduction of blood and blood product screening remains a priority.
HEMODIALYSIS
Infection with HCV is endemic in hemodialysis units, especially in Middle Eastern countries [31-33]. HCV transmission in this setting has been described since the late 1960s [34-38]. The prevalence of HCV in patients on dialysis varies greatly by geographic area, and also in different centers within the same region [31,39-41]. The factors that were constantly reported as being associated with an increased prevalence of HCV infection were the length of time on dialysis and the number of blood transfusions received. The introduction of anti-HCV blood donor testing and the use of erythropoietin to reduce transfusion requirements have not completely eliminated infection, but a significant reduction has been achieved. Experts agree that the scrupulous application of universal hygiene precautions is essential in avoiding patient-topatient transmission [42-46]. However, there is no consensus in the nephrology community concerning the isolation of infected patients and the use of dedicated dialysis machines to prevent HCV infection [31,44].
Outbreaks of HCV infection have been observed in chronic hemodialysis, hospital inpatient, and private practice settings. These outbreaks are associated with use of contaminated equipment and unsafe injection practices, including reuse of disposable needles and syringes and contamination of multiple-dose medication vials [44]. The spread of HCV has been associated with inadequate staff training and a higher baseline prevalence of infection in the facility.
ORGAN TRANSPLANTS
The prevalence of HCV infection in organ donors is difficult to determine and varies greatly by geographical location. Based on this, and although the actual risk of transmission via transplants is low, it is recommended that HCV-positive persons not donate organs, other tissues, or semen [47,48].
OCCUPATIONAL EXPOSURE
The risk of health care workers becoming infected through occupational exposure is reported in a separate chapter in this issue.
Health care worker to patient transmission
The transmission of HCV from HCV-infected health care workers to patients has been documented in a limited number of individual cases and clusters [49,50]. These were associated with medical procedures, including the use of contaminated multi-dose vials, spring-loaded finger sticks, surgical interventions, and gastrointestinal endoscopy [51-54]. Since these cases have mainly occurred as clusters, no comprehensive and reliable estimates of nosocomial risks are available, but studies of patients with acute and primary HCV infection suggest that a contaminated health care environment may be responsible for a substantial number of cases, especially in areas and settings with higher endemic rates of HCV [55,56]. Even though this mode of transmission is currently considered to be very rare - at least in developed countries [57-59] - it is an issue with complex ethical and forensic implications including a possible restriction of access to certain medical professions or the application of professional restrictions for health care workers [60,61].
ILLICIT DRUG USE
Illicit use of intravenous drugs is now the main source of HCV infection in most developed countries and is becoming a major source of infection in transitionaleconomy and developing countries [62,63]. In published surveys the rate of HCV infection in illicit intravenous drug users ranges from 48 to 96% [64-66], and the prevalence of HCV infection is appreciably higher than that of either HBV or HIV infection [67]. The prevalence of anti-HCV increases with the duration and intensity of intravenous drug use [68], but there is a distressingly high HCV infection rate of 5 - 20% within the first 6 -12 months of drug injection [69,70]. However, it should be noted that in certain settings the risk of HCV acquisition among drug users has been reduced as a result of changes in injection practices that minimize sharing of contaminated equipment through involvement in needle and syringe exchange programs [71-78].
Unsafe injection practices
Unsafe injection practices have raised little interest thus far and their consequences are therefore largely unknown to the public and even among many health care professionals.
In the past, mass immunization campaigns using poorly sterilized syringes and unscreened blood and blood products were excellent vectors for the transmission of infectious diseases including HCV. Anti-schistosomal treatment using injectable antimony was responsible for the dissemination of HCV among the general populations in Japan and Egypt; the epidemic in Egypt persisted until 1986, resulting in the world's highest national seroprevalence of anti-HCV antibody [79,80].
Besides mass immunization campaigns and unsafe injection practices, one issue has not yet been sufficiently addressed and remains a major problem: the WHO estimates that approximately 16 billion injections are administered worldwide each year (only 10 % of them related to vaccination), and that in developing countries 6.7 billion unsafe injections are administered (39.3% of all injections). This contributes to more than 2 million HCV infections per year and results in 200,000 HCV-related premature deaths and 3.6 million years of human life lost [81]. The highest reported rates of needle re-use are found in the Middle East, southeast Asia and western Pacific countries [82]. The distribution of infection within populations is highly clustered, with the average number of infections per year ranging from 0.9 to 8.5 in different countries [83]. The use of contaminated injection equipment causes a steady number of unrecognized transmissions on a daily basis. This ongoing iatrogenic transmission of HCV infection occurs mainly in poor regions of the world and has 2 main causes: the reuse of injection devices, mainly due to financial constraints, and the administration of unnecessary injections [84,85]. A number of studies have demonstrated that most of the parenteral treatments administered in developing countries are unnecessary, and that there is a substantial association between HCV seropositivity and the use of unsafe health care devices [82].The most frequently injected medications include antibiotics, vitamins and analgesics that could be taken orally; as well, these are commonly used for nonspecific symptoms such as headache, fatigue, nausea, myalgia or fever. The injections and equipment are frequently purchased outside the formal health care system and administered by unqualified personnel in pharmacies and marketplaces.
To reduce these unacceptable practices, the community, health care systems, governments and health organizations must agree on and emphasize the use of disposable medical supplies, the sterilization of reusable supplies and equipment, and strict adherence to and enforcement of safe and standard medical practices [86,87]. There is a need for policies and plans for the safe and appropriate use of injections in countries where practices are substandard. Other issues include staff work overload, administrative pressures to reduce costs, and lack of proper supervision of personnel [88].
CONCLUSION
In developed countries, the use of blood transfusions has reached an unprecedented level of safety with regard to HCV transmission. The risk of acquiring transfusiontransmitted hepatitis C is now marginal, but there are still reports of cases and clusters of iatrogenic HCV transmission associated with medical practices mainly due to breaches of infection-control standards.
The situation is completely different in the less developed regions of the world, where several million people acquire HCV infection each year as a result of contaminated blood transfusions and unsafe injection practices. The uncontrolled HCV epidemic in developing regions is a cause of great concern. The patterns of viral spread in these areas follow the ones observed previously with HBV and HIV, and will probably contribute to increasing morbidity and mortality.To effectively combat the global epidemic of HCV and other blood-borne infections, it is essential to eradicate the widespread practice of unsafe medical procedures. Much of this task lies in the hands of developed countries, with the design and implementation of comprehensive and interdisciplinary safety interventions [23,48]. Unfortunately, for the time being, the iatrogenic epidemic of hepatitis C will continue to spread in many regions of the world.
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