Top PDF Hepatitis C virus infection in blood donors from the state of Puebla, Mexico

Screening of blood donors was performed using the AxSYM HCV 3.0 assay (Abbott Diagnostics, Wiesbaden, Germany). The AxSYM HCV 3.0 is an indirect micro- particle enzyme immunoassay (MEIA) that detects human antibodies against recombinant HCV proteins core, NS3, NS4, and NS5. The values of antibody detec- tion are expressed as the ratio between the signals detected in the sample and the cutoff value (S/CO); samples with S/CO values ≥ 1.0 were considered reac- tive [22]. All reactive samples were submitted to a sec- ond anti-HCV detection test.

In the United States seroprevalence in HCV of blood donors was estimated to be 0.3 percent. [22] In Greece also, a low prevalence (0.2 to 0.4%) of antibodies to HCV has been reported and a similarly low rate (0.13%) was also reported from Iran. Lower rates of anti-HCV antibodies have also been reported in blood donors of Turkey (0.07%), Saudi Arabia (0.4%), Mexico (0.84%) and Kenya (0.9%). [22] HCV is globally distributed, with anti-HCV prevalence among donors ranging from 0.3 to 0.5% throughout the world. [18] Prevalence of HCV in blood donors calculated in our study is found to be lower than most other incidence studies all over India (0.11% vs. 0.53 to 5.1%). [4] The low prevalence of HCV in blood donors in Madhya Pradesh was may be due to proper screening of donors and strict follow up of donor questionnaire which eliminated the high risk donors. When analyzed year wise, a decrease in HCV reactivity among blood donors was reported from 2014 to 2015. This change was attributed to proper donor selection with counseling and filing up of questionnaire. In 2017 a slight increase was noted in HCV incidence which most likely occurred due to introduction of advanced technique for detection which curtail the false negative results observed in the window period and increased sensitivity.

Huang et al, carried out the molecular characterization of HBV from OBI cases in a cohort of blood donors (n = 38.499). The analysis of the ORF S showed a higher frequency of mutations in MHR (aa 110–160) in OBI cases compared to the donor HBsAg + (Chronic infec- tion). Interestingly, the MHR mutation frequency was not correlated with the serum level of HBsAg. Thirteen MHR mutations (G119R, P120T, C124R, C124Y, I126S, Q129R, S136P, C139R, T140I, K141E, D144A, G145A, and G145R) were detected and functionally character- ized in vitro and in vivo. Some of these mutations, in- cluding K141E, impaired the secretion of virions and subviral particles and reduced the reactivity of antibodies anti-HBs used in immunoassays [35]. In the present study was also described a mutation at position 141 (sK141N).

even cirrhosis and Hepatocellular Carcinoma. [5] Normal ALT level ranges between 7-56 U/L with slight variation in individual laboratory’s reference values and ALT level >56 U/L considered high and abnormal. [6-7] Persistently normal ALT (PnALT) defined as ALT level less than upper normal limits on three bimonthly consecutive serum levels for the period of six month. [8] Indeed the accuracy of normal ALT to predict normal histology or any change related to HCV infection is still vague. [9] Considering the truly healthy HCV positive blood donors, this study was conducted in healthy family blood donors who are incidentally found anti HCV reactive on Screening and also having HCV RNA positive, with normal ALT. Liver biopsy always have some risk and complication as 84% have mild discomfort, 20% have pain, 0.3% have serious complication while 0.01% reported death. [10]

Concealing of medical history by captive, paid or professional blood donors, who widely exist in developing countries, also pose a great threat to safe blood supply. There is a long list of viruses, parasites and bacteria, which can be transmitted through blood transfusions. Among them, important transfusion-transmitted viruses are human immunodeficiency virus (HIV-I/II), hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis infection by spirochytes and transfusion associated malaria infection (25) . CHIKV transmission through

Netherlands, which may indicate a geographically confined circu- lation of endemic HEV strains within Germany and neighboring countries. A more detailed analysis of the sequences showed that most of the donor-derived sequences were closely related to HEV sequences from pigs, thus suggesting zoonotic transmission from pigs to humans as a major mode of infection. It has been shown that the anti-HEV IgG seroprevalence almost doubles in individ- uals with frequent contact to swine and other animals, e.g., slaugh- terers, veterinarians, and farmers (12, 28). Two of the strains showed very high percentages of sequence identity to an HEV strain detected in a porcine liver sold at a market in Germany (45), supporting the hypothesis of food-borne HEV infections. How- ever, as pigs and pig products are the subject of extensive trade between countries worldwide, the distinct geographical origin of the pig HEV strains often remains unclear. It is therefore of special interest that the largest evolutionary cluster, containing nine se- quences of the donors, also includes the wild boar strain Wb- GER17 (Fig. 1, Wb-DE-2006, indicated by an asterisk). This strain was originally detected in 25.9% of wild boar livers originating from a distinct region in Brandenburg, Germany, in 2006 (43). It could be speculated that these wild boars serve as a local reservoir for HEV, from which the virus could be transmitted directly or indirectly via infection in pigs to susceptible humans. Further analysis of samples from wild boars, pigs, and humans, including more-detailed geographical data, are necessary in order to under- stand the epidemiology of HEV infections. Most importantly, many of the strains detected in the donor samples showed up to 98% nucleotide sequence identity with the corresponding region of strains derived from human clinical hepatitis E cases. This find- ing may indicate that the detected strains are capable of inducing disease under certain conditions.

Hepatitis B virus (HBV) was among the first virus known to be transmitted by blood and blood products. HBV infection from transfusions became rare after the introduction of the HBsAg test in early 1970, but remains one of the most common serious complications of transfusion particularly in countries with high and intermediate prevalence of HBV [1-4]. The residual transmission risk of HBV through transfusion is higher [5-8]. This is attributed to the interval between initial HBV infection and the detection of hepatitis B surface antigen (HBsAg), resulting in a long window phase dur- ing which the virus is transmissible [9,10]. After the implementation of HBsAg screening in the 1975s, there have been no further measures in Albania to decrease

cirrhosis, chronic hepatitis, and hepatocellular carcinoma [7, 8]. Some important ways for the transmission of HBV are the utilization of unsterilized medical instruments, blood transfusion, sharing of individual items, offering needles to drug addicts, barber risk, reuse of contaminated needles and syringes without sterilization for therapeutic injections, vertical transmission , furthermore by unsafe sexual interaction with HBV infected patients [9-12]. The prevalence of HBV infection among the developing countries of Asia, the Pacific Islands and Africa is very high as compared to developed countries like Australia, Western Europe, and the USA, where the prevalence of HBV is very low [13]. In Russia, Japan, and Eastern Europe about 2- 8% of their population are infected with HBV. It is estimated by world health organization (WHO), that about 0.6 million deaths of the people occur annually due to HBV infection. As per 2010 report of WHO, it was observed that 0.12 billion individuals were infected with HBV in China followed by India with 0.04 billion and Indonesia with twelve million infected individuals [14]. In Pakistan, HBV is also a prominent public health issue, and its rate of infection is rising rapidly [15]. The reason for high infection rate might be due to deficiency of suitable public health services, poor financial condition or lack of awareness about the transmission of major sexually transmitted diseases (STDs) i.e. HBV, HCV, and HIV [16]. According to different research studies performed in the various regions of Pakistan, showed that the prevalence rate of HBV is 2- 10% among healthy blood donors, 5-9% among medical services staff, 3.16% among the pregnant women, 3.6-18.66% among the general population, 10-20% of patients with temporary diagnosis of hepatitis and 3.16- 10.4% among professional blood donors [17].

Genotype 2 isolates from donors and patients displayed a typical “endemic” profile, with a large number of subtypes (11 genotype 2 subtypes) and few isolates in each subtype. Infection by type 2 was also associated with the older age bracket in our study. Remarkably, type 2 accounted for more than 20% of strains collected before 1995 but was never found between 2001 and 2002. This finding suggests that this endemic genotype is progressively being replaced by epidemic genotypes. The most prevalent subtypes were 2a, 2b, 2c, 2i, and 2k, all of which presented more than three strains each. Among the various subtype 2 isolates found in our study, two, i.e., subtypes 2i and 2l, were exclusive to FIG. 2. Distribution of hepatitis C virus types according to date of collection. The number of cases is indicated in parentheses.

Given that HBV and HCV have the same transmission routes, co-infection may occur in an estimated 7- 20 million individuals infected with both viruses worldwide [35]. In the present study, 7 samples (0.1%) were seropositive for both HCV and HBV but only one sample (0.018%) was positive for both viruses using PCR. The exact prevalence of HBV and HCV co-infection is not known because most of the published reports focused on highly selected and limited populations. Multiple studies evaluated the rates of HCV co-infection among HBsAg carriers; the rates range from 1.3% to 18%, depending on the

From January 2000 to December 2010, Korean Red Cross Blood Centers collected a total of 25,931,924 donations. Repeat donors accounted for 20,914,785 donations (80.7%). During the study period, a total of 43 HIV-positive (2004–2009), 139 HCV-positive (2000– 2009), 629 HBV-positive donors (2000–2009) were clas- sified as seroconvertors (Table 3). The residual risk for HCV decreased throughout the study period (p = 0.001). The residual risk of HIV was estimated at 1 in 1,080,244 in 2004/2005 and at 1 in 1,813,998 in 2008/2009 (p = 0.745). The residual risk of HCV decreased continu- ously from 1 in 81,431 in 2002/2001 to 1 in 4,560,879 in 2008/2009, which is extremely low like that of HIV. The residual risk of HBV was estimated at 1 in 67,826 in 2008/2009 (p = 0.885), which is more than 20 times higher than other viruses (Table 3). The incidence rates among first-time and repeat donors were 1.0 and 2.0 for both HIV and HCV (Tables 4 and 5). The most recent (2009/2010) residual risk of transfusion-transmitted in- fection in Korea was estimated to be 1 in 1,356,547 Table 2 Donor screening tests for HIV, HCV, and HBV from 2000 to 2010

This can be achieved by providing the screening protocols of the safe blood donation. Supplying safe blood has been considered as a great concern in some less-developed and developing countries where donors are paid for whole blood collection. Paid donors are mostly from poor economic and social groups selling blood to earn money. This payment system can increase the transmission risk of blood-borne viruses 2 .

The importance of sexual activity in the transmission of HCV has not been well-established [37]. Nevertheless, studies with blood donors suggest an association between sexual transmission and HCV [10,11,17,31,40]. This study detected an independent association between sexu- al behavior and positive anti-HCV test. The results of the logistic regression model show that the number of sexual- ly transmitted diseases during life and sexual intercourse with injection drug users and with HBV or HCV carriers were independent risk factors for anti-HCV positivity. Even though number of sexual partners and sexual orien- tation were associated in the bivariate analysis, they were not independent of other risk factors such as transfusion and injection drug use by the donor or his/her sexual part- ner. In South America, the prevalence of HCV infection in heterosexuals attending STD clinics and with no history of injection drug abuse (11.5%) is greater than in North America (6.0%) and Europe (1.9%) [37]. It is speculated that HCV transmission may be facilitated by sexually transmitted diseases [41,42]. However, there is a possibil- ity that HCV seropositivity associated with sexual inter- course with injection drug users or HBV/ HCV carriers may result from actual sexual transmission of HCV – al- though it may also result from exposure to unreported parenteral risk factors or from sharing certain personal items, such as toothbrushes or razors, which can result in accidental exposure to the partner's blood [11,33,42]. In conclusion, this case-control study confirmed some in- dependent risk factors for anti-HCV positive test described in other studies of blood donors. The hierarchical multi- variate analysis identified age, schooling, incarceration, past transfusion, tattooing, intravenous drug use, number of sexually transmitted diseases, sexual intercourse with injection drug users and partners with hepatitis B or C as the main risk factors for HCV seropositivity in the present population of southern Brazilian donors. Some character- istics of sexual behavior were detected as independent risk factors, suggesting that sexual intercourse is an important source of transmission. The identification of groups at risk and the planning of interventions aimed at controlling HCV infection should take these findings into account. Competing interests

Hepatitis C virus (HCV) is a serious global public health problem is one of the most frequent infections associated with blood transfusion [1]. It has been reported that, HCV responsible for 90- 95% of post transfusion, previously known as Non A Non B (NANB) transfusion-related hepatitis [2,3]. The estimated prevalence of HCV infection worldwide is 2.8% [4], whereas 3 to 4 million people are newly infected each year [2,3,5] and 2% of the world’s population have chronic HCV infection [4].

The uneven distribution of age between healthy donors and NAT-positive donors could be related to changes in risks of these pathogens in the general population. Teen- age children and young adults in the 1960s and 1970s (who were over 40 years old between 2010 and 2012) might have received transfusions or medical procedures with non-disposable needles and thus might have become infected with HCV. The increase in HIV prevalence among donors between 30 and 40 years of age since 2000 could reflect the change in perception among the public about HIV threat and could have therefore led to a more relaxed control of HIV transmission. For example, some people might have mistakenly believed that available treat- ment for HIV infection is effective and thus might have engaged in more risky behavior, which could have resulted in the recent increase in new infections among men who have sex with men in certain areas [41,42]. These results are consistent with those obtained in previous studies [25,28,43].

Transmission of HBV results from exposure to infectious blood and bodily fluids, blood transfusions and blood products using unscreened blood, medical or dental intervention without adequate sterilization of equipment, sharing equipment for injecting drugs, sharing straws and notes for snuffing cocaine, sharing razors, toothbrushes or other household articles, tattooing and body piercing if done using unsterilized equipment and vertical transmission from mother to child [4] . Without intervention the risk of perinatal HBV transmission is greatest for infants born to women who are hepatitis B surface positive [5]. There are three mechanisms of HBV transmission from HBsAg positive mothers: (i) trans-placenta intra-uterine transmission; (ii) during delivery by contact with maternal infected fluids in the birth canal; and (iii) post natal transmission from mother to child through breastfeeding or during child birth [6]. Children who do not become infected during the perinatal period remain at high risk of infection during early childhood [7]. HBV-related end-stage liver disease or hepatocellular carcinoma (HCC) are responsible for over one million deaths per year and currently represent 5 − 10% of cases of liver transplantation[8,9,10]. Nigeria has remained a hyper-endemic area for hepatitis B virus infection, with an estimated 12% of the total population being chronic carriers, despite the existence of a safe and effective vaccine [11].

Determination of the prevalence of liver disease caused by hepatitis C virus (HCV) of various genotypes helps provide an understanding of the virulences of these genotypes. Differences in the prevalences of these genotypes are known to exist in the various geographical regions of the world. Hence, we performed seroepi- demiological and molecular epidemiological analyses of HCV in Surabaya, Indonesia. The prevalences of anti-HCV antibodies were 2.3, 76.3 and 64.7% in healthy blood donors, patients on maintenance hemodialysis, and patients with hepatocellular carcinoma (HCC), respectively. HCV-2a was the most common (52%) among the HCV clones obtained from blood donors; this was followed by HCV-1b (15%), HCV-1a (7%), and HCV-1d (7%), a unique Indonesian subtype. The high prevalence of HCV-2a in blood donors was further supported by serotyping analysis that could discriminate HCV type 2 (HCV-2a and -2b) from HCV type 1 (HCV-1a, -1b, and -1d). HCV-1a, -1b, and -1d were strongly associated with elevated serum alanine aminotransferase (ALT) levels in blood donors, suggesting a possibly more pathogenic feature of those subtypes than HCV-2a. In patients on maintenance hemodialysis, HCV-1a and -1b (each 31%) were among the most common subtypes, and in contrast to the case with blood donors, HCV-1a, -1b, and -1d were found in those with normal ALT as well as those with elevated ALT levels. Impaired immune responses of hemodialyzed patients might be responsible for the apparently decreased hepatocytic injury caused by infection with HCV type 1. In patients with HCC, HCV-1b (57%) was the most common; this was followed by HCV-1d (19%) and HCV-2a (5%). Subtype prevalence was not different between HCC patients with advanced liver cirrhosis and those without advanced cirrhosis.

drug users (IVDU) and tattooing. Despite that 29(28.2%) and 14(13.6%) of blood donors had history of intravenous drug abuse (IVDU) and tattooing, but there was no significant association between HCV genotypes and mode of transmission (P=0.9). Genotypes 1a and 3a most often infect injecting drug abusers and appear to be increasing in prevalence (23-24).Genotype 1b was seen in four blood donors (3.9%). Genotypes 1b and 2a are most strongly associated with infected blood products and the relative prevalence of these genotypes has decreased in the recent years due to improved blood screening (25-26). Mocmish et al investigated on infected volunteer blood donors from nine countries (Scotland, Finland, The Netherlands, Hungary, Australia, Egypt, Japan, Hong Kong, and Taiwan).They showed the presence of genotypes 1, 2, and 3 for almost all infections in donors from Scotland, Finland, Netherlands, and Australia (27). They reported that genotypes 2 and 3 were not found in the eastern European country (Hungary), where all but one of the donors was infected with type 1(27). Donors from Japan and Taiwan were infected only with type 1 or 2, while types 1, 2, and 6 were found in those from Hong Kong. HCV infection among Egyptians was almost always by type 4 (27). The genotype distribution of hepatitis C virus (HCV) in blood donors from southeast France showed that the most frequent genotypes were 1b (30.2%), 1a (27.7%), and 3a (22.4%)(28).In another study in Brazil country, the proportions of blood donors with HCV types 1, 2, and 3 were 70.0%, 2.9%, and 25.7%, respectively(29). The study on HCV genotypes among blood donors in Korea showed that HCV genotype 1b was most dominant (80%), followed by genotype 2a (13.3%), and 2b (6.7%) (30). Therefore, distribution of genotypes HCV in infected blood donors in Iran is similar to epidemiological data from West Europe.

Our study has several limitations. First, a small number of patients with recent HCV infection were identified, which substantially limited the statistical power of the study to assess associations and make meaningful comparisons. The second possible limitation is the relatively short dur- ation of follow-up. It is well established that the vast major- ity of patients with spontaneous clearance after acute HCV infection clear the virus within 6 months of infection, [3, 4] subsequently we limited the follow-up in our study to 24 weeks. However, there are reports showing viral clear- ance after 6 and even 12 months periods even in patients with established chronic infection [31–33]. Thus it is pos- sible that we missed some patients who might have cleared the virus after the end of follow-up. Our study was not powered to evaluate immunological aspects of recent HCV infection, which might have provided explanations for rare clinical cases seen in this study. Finally, it is now clear that interleukin 28B (IL28B) plays an important role in spontan- eous clearance of acute HCV, [34] but unfortunately stored samples have not been available to test for IL28B retrospectively.

Transfusion of blood and blood product is a life- saving measure and benefits numerous patients worldwide. However, transfusion is an important mode of transmission of infection to the recipients. In 2005, all member states of WHO signed a document that commits them to the provision of safe and adequate blood and blood products to patients [1]. Transfusion-transmitted infectious diseases remain a major topic of interest for those involved in blood safety [1]. To avoid infection by blood transfusion, safety is very important because of blood transfusion is an integral part of medical and surgical therapy. Therefore, the tests for HIV, HBV, HCV syphilis and malaria are mandatory in the blood bank [2]. Hepatitis B virus (HBV), hepatitis C virus (HCV) are a major global public health problem warranting high priority efforts for prevention, control and treatment [3]. Testing for hepatitis B surface antigen (HBsAg) is the commonly used screening test in developing countries [4]. The hepatitis C virus was discovered in 1989. It is transmitted via blood and blood products, both parenterally and through sexual contact [5]. Libya, a developing country of approximately 6 million people, belongs to the intermediate endemicity countries with a wide variance of sero-positivity among different regions and populations [6]. A national serological survey for HBV and HCV infections among the general population was performed in Libya during 2003 and revealed prevalence of 2.2% and 1.2% for HBV and HCV, respectively [7]. A local surveys reported that the rate of HBsAg positivity among blood donors ranged from 1.3% to 4.6% [8], while the rate of HCV antibodies was 1.2% [9,10]. Very recently, the frequency of HBsAg positive blood donors and anti-HCV among this sample was 0.8% and 0.7% respectively in blood donors in western Libya (Tripoli) [11]. There has