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1.  Study on effectiveness of transfusion program in thalassemia major patients receiving multiple blood transfusions at a transfusion centre in Western India 
Background:
Children suffering from beta-thalassemia major require repeated blood transfusions which may be associated with dangers like iron overload and contraction of infections such as HIV, HCV, and HBsAg which ultimately curtail their life span. On the other hand, inadequate transfusions lead to severe anemia and general fatigue and debility.
Materials and Methods:
Data were obtained from 142 beta-thalassemia major patients aged 3 years or more receiving regular blood transfusions at a transfusion centre in Western India from 1 April 2009 to 30 June 2009. The clinical data and laboratory results were subsequently analyzed.
Results:
Of the 142 patients, 76 (53.5%) were undertransfused (mean Hb <10 gm%). 96 (67%) of the patients were taking some form of chelation therapy but out of them only 2 (2%) were adequately chelated (S. ferritin <1000 ng/ml). 5 (3.5%) of the patients were known diabetics on insulin therapy. 103 (72%) of the patients were retarded in terms of growth. The prevalence of transfusion-transmitted infections (TTIs) such as HCV, HIV, and HBsAg was respectively 45%, 2%, and 2%, with the prevalence of HCV being significantly more than the general population. The HCV prevalence showed positive correlation with the age of the patients and with the total no of blood transfusions received. As many as 15% (6 out of 40) children who were born on or after 2002 were HCV positive despite the blood they received being subjected to screening for HCV.
Conclusions:
The study suggests the need to step up the transfusions to achieve hemoglobin goal of 10 gm% (as per the moderate transfusion regimen) and also to institute urgent and effective chelation measures with the aim of keeping serum ferritin levels below 1000 ng/ml to avoid the systemic effects of iron overload. In addition, strict monitoring of the children for endocrinopathy and other systemic effects of iron overload should be done. Rigid implementation of quality control measures for the ELISA kits used to detect HCV in donor blood needs to be done urgently. Alternately, more sensitive and specific measures (like NAT testing) should be employed for detection of HCV. In the absence of a definitive cure accessible and available to all patients, strict implementation of the above suggested measures will go a long way in improving the quality (and quantity) of life in patients of beta-thalassemia major.
doi:10.4103/0973-6247.67029
PMCID: PMC2937304  PMID: 20859507
Beta-thalassemia major; chelation; HCV positivity; iron overload
2.  Prevalence of Hepatitis B and C Infections and HCV Genotypes Among Haemophilia Patients in Ahvaz, Southwest Iran 
Background
Transfusion-transmitted hepatitis is the most important cause of transmitted infections by the parenteral route in patients with haemophilia.
Objectives
This study was performed to determine the prevalence of HBV, HCV, and different genotypes of HCV among haemophilia patients in Ahvaz city, southwest Iran.
Patients and Methods
A cross-sectional study was conducted on 87 haemophilia patients referred to the Hemoglobinopathy and Thalassemia research centre during February 2008 to March 2009. Patients, sera were tested for HBsAg and anti-HCV using ELISA and confirmed by PCR (HBV) and RT-PCR (HCV). HCV genotypes were determined with HCV genotype specific primers using HCV genotyping kit.
Results
The overall prevalence rate of HBsAg and anti-HCV were 1.1% (95% CI: 0-3.39) and 54% (95% CI: 43.5-64.4), respectively. Forty two of the anti-HCV patients (89.3%) were also HCV RNA positive. The prevalence of anti-HCV seropositivity was significantly higher (P = 0.0008) among patients who had started to receive transfusions before implementation of blood donor screening. Moreover, the number of transfusion were significantly associated with anti-HCV and HCV RNA positivity (P = 0.0041 and P = 0.023, respectively). The predominant HCV genotype among haemophilia patients in our region was 1a (26/42, 61.9%), although genotypes 1b and 3a were found in 26.1% (11/42) and 11.9% (5/42) of the patients, respectively.
Conclusions
It appears stringent donor selection procedures reduced HCV infection in multi-transfused patients, but it is still serious risk for these subjects.
PMCID: PMC3470840  PMID: 23105982
Hepatitis B; Hepatitis C; Prevalence; Genotype; Haemophilia A
3.  Prevalence of Hepatitis C among Multi-transfused Thalassaemic Patients in Oman 
Objectives:
Regular blood transfusions are essential for patients with thalassaemia major. However, infections with hepatotropic viruses remain a major concern. The objective of this study was to evaluate the prevalence and characteristics of hepatitis C viral (HCV) infection among patients with homozygous beta thalassaemia in a single centre in Oman.
Methods:
A retrospective chart review of 200 patients treated at the Thalassemia Unit of Sultan Qaboos University Hospital (SQUH) in Muscat, Oman, between August 1991 and December 2011 was performed. Relevant demographic and clinical characteristics were collected, including age, gender, HCV status and the presence of endocrinopathies.
Results:
A total of 81 patients (41%) were found to be anti-HCV-antibody (anti-HCV)-positive. HCV ribonucleic acid tests were performed on 65 anti-HCV-positive patients and were positive among 33 (51%); the remaining 16 patients died before these tests were available. Anti-HCV-positive patients were significantly older than anti-HCV-negative patients (P <0.001) and were more likely to be diabetic than anti-HCV-negative patients (27% versus 8%; P <0.001). A total of 100 patients had been transfused before they were transferred to SQUH in 1991; of these, 70 (70%) were anti-HCV-positive. Only 11 (11.5%) of the 96 patients who were seronegative in 1991, or who were transfused later, became seropositive.
Conclusion:
It is likely that the high prevalence of HCV among multi-transfused thalassaemic patients in Oman is due to blood transfusions dating from before the implementation of HCV screening in 1991 as the risk of HCV-associated transfusions has significantly reduced since then. Additionally, results showed that anti-HCV-positive patients were more likely to be diabetic than anti-HCV-negative patients.
PMCID: PMC4318606
Hepatitis C; Anti-HCV Antibodies; Beta Thalassemia; Seroprevalence; Blood Transfusions; Blood Safety; Oman
4.  Torque Teno Virus and Hepatitis C Virus Co-Infection in Iranian Pediatric Thalassemia Patients 
Turkish Journal of Hematology  2013;29(2):156-161.
Objective: Torque teno virus (TTV) infects patients at risk for parenteral exposure and chronic blood transfusion, such as those with β-thalassemic. This study aimed to assess the prevalence of TTV infection and co-infection of TTV and hepatitis C virus (HCV) in pediatric thalassemia patients receiving chronic blood transfusion.
Material and Methods: The study included 90 pediatric thalassemia patients receiving chronic blood transfusion that presented to the Mofid Children’s Hospital, Tehran, Iran. The control group included 90 healthy volunteer children. Serum TTV DNA detection via semi-nested PCR and HCV Ab were performed in all the participants. Demographic characteristics and clinical data were collected from each participant for statistical analysis.
Results: In all, 64.4% of the patients had TTV infection, versus 24.4% of the controls (P < 0.01). The thalassemia patients had a greater probability of having TTV and HCV infections than the controls, with a common OR of 5.60 (95% CI: 2.94-10.69) and 2.15 (95% CI: 1.83-2.50), respectively. In total, 17.2% (10/58) of the patients that were TTV positive were also HCV positive, whereas 6.3% (2/32) of the TTV-negative patients were anti-HCV antibody (Ab) positive (P = 0.14).
Conclusion: The prevalence of TTV and HCV infection was higher in the Iranian thalassemia patients on chronic transfusion therapy than in the controls. The high prevalence of TTV in pediatric thalassemia patients on chromic transfusion therapy may indicate the superiority of the parenteral route compared to other routs of TTV transmission.
doi:10.5505/tjh.2012.20280
PMCID: PMC3986954  PMID: 24744647
Thalassemia; Torque teno virus; Hepatitis C virus
5.  Transfusion Transmitted Hepatitis: Where Do We Stand Now? A One Center Study in Upper Egypt 
Hepatitis Monthly  2012;12(4):286-291.
Background
Despite progress made in the prevention of transfusion-transmitted infections (TTI) over the last few years, they continue to be a problem in many parts of the world, particularly in multitransfused patients.
Objectives
The aim of this study was to estimate the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and to evaluate the screening and vaccination program among our cohort of multitransfused children from Qena, Upper Egypt.
Patients and Methods
One-hundred children suffering from diseases requiring repeated blood transfusions were included in the study. They were classified into group 1, which included 67 children with thalassemia, and group 2, which included 33 children with hemophilia. Screening for hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody and antibody to HCV was done using a second-generation enzyme-linked immunosorbent assay technique.
Results
Only 12% of all patients were either acutely or chronically infected with HBV. 46% were immune due to previous vaccination, whereas 39% of patients were not protected from HBV infection. HCV antibodies were positive in 45% of cases. Seventy-eight patients had a complete hepatitis B vaccination in the form of three doses as documented by birth certificate. Thirty-six patients mentioned history suggestive of hepatitis. The prevalence of the studied hepatitis markers was similar in both the thalassemia and hemophilia groups of children.
Conclusions
Transfusion-transmitted hepatitis is still a major problem for multitransfused children in Egypt. More effort is required to reduce the infection rate through proper screening of blood and blood products, strict emphasis on receiving the vaccine, regular follow-up for those children with a hepatitis B antibody titer, and providing booster doses for those in need.
doi:10.5812/hepatmon.852
PMCID: PMC3360939  PMID: 22690237
Child; Hepatitis; Transfusion; Egypt
6.  Prevalence and trends of markers of hepatitis B virus, hepatitis C virus and human Immunodeficiency virus in Argentine blood donors 
BMC Infectious Diseases  2014;14:218.
Background
Transfusion-transmitted infections are a major problem associated with blood transfusion. The aim of this study was to determine prevalence and trends of HBV, HCV and HIV in blood donors in Argentina.
Methods
A retrospective study was carried out in blood donors of 27 transfusion centers covering the whole country over a period of eight years (2004-2011). Serologic screening assays for HBsAg, anti-HBc, anti-HCV, and anti-HIV were performed in all centers and nucleic acid amplification testing (NAT) was performed in 2 out of the 27 centers.
Results
The 2,595,852 samples tested nationwide from 2004 to 2011 showed that the prevalence of HBsAg decreased from 0.336% to 0.198% (p < 0.0001), that of anti-HBc from 2.391% to 2.007% (p < 0.0001), that of anti-HCV from 0.721% to 0.460%, (p < 0.0001) and that of anti-HIV from 0.208% to 0.200 (p = 0.075). The prevalence of HBV, HCV and HIV was unevenly distributed among the different regions of the country. Two out of 74,838 screening- negative samples were positive in NAT assays (1 HIV-RNA and 1 HCV-RNA); moreover, HBV-DNA, HCV-RNA and HIV-RNA were detected in 60.29, 24.54 and 66.67% of screening-positive samples of the corresponding assays. As regards donors age, positive HBV-DNA and HCV-RNA donors were significantly older than healthy donors (46.6, 50.5 and 39.5 y respectively, p < 0.001).
Conclusions
Argentina has a low prevalence of HBsAg, anti-HCV and anti-HIV in blood donors, with a decreasing trend for HBsAg, anti-HBc and anti-HCV but not for anti-HIV over the last 8 years. The uneven distribution of transfusion-transmitted infections prevalence among the different regions of the country highlights the need to implement regional awareness campaigns and prevention. The discrepancy between samples testing positive for screening assays and negative for NAT assays highlights the problem of blood donors who test repeatedly reactive in screening assays but are not confirmed as positive upon further testing. 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 and might be attributed to a longer exposure to transmission risk factors in elderly people.
doi:10.1186/1471-2334-14-218
PMCID: PMC4018657  PMID: 24755089
Prevalence; Trend; Blood donors; HIV; HBV; HCV
7.  Serological study on parvovirus B19 infection in multitransfused thalassemia major patients and its transmission through donor units 
Background:
Human parvovirus B19 (B19) virus is a newly recognized agent for transfusion transmitted diseases. Beta-thalassemia major patients receive a hypertransfusion regimen, hence, are prone to acquire B19 infection; moreover, B19 escapes viral inactivation methods and donor units are not tested for B19, but there are just a couple of studies globally and none from the Asian continent. Hence, a study was designed to find the frequency of B19 infection and its transmission in multitransfused thalassemia patients.
Materials and Methods:
Ninety multitransfused beta-thalassemia major (thalassemia) patients, 32 controls (age, sex matched) without any history of transfusion were enrolled. Besides the donor units were tested in B19 un-infected patients. B19 specific IgG and IgM antibodies in the sera were analyzed by ELISA (in-house), using B19 VPI and VP2 recombinant and purified antigens; additionally HBsAg and anti-HIV and anti-HCV antibodies were tested for coexisting infections.
Results:
Seventy-three (81%) thalassemia patients tested positive for anti-B19 IgG antibodies as compared to seven (21%) in the controls group (P < 0.01), while anti-B19 IgM antibodies were detected in 37 (41.1%) compared to two (6.2%) in the controls (P < 0.01). Mean age of the thalassemia patient was eight years (range 2 – 18 years) and B19 infection was highest in the six-to-ten year range. Seropositivity increased with the number of transfusions. Two of the four HBsAg positive and five of the seven anti-HCV IgM antibody-positive patients also had anti-B19 IgM. After a six-month follow-up, four (25%) of the 16 seronegative patients seroconverted and anti-B19 IgM antibodies were detected in their donor units.
Conclusions:
Most of multitransfused thalassemics were B19 seropositive or had anti-B19 IgM; in the remaining uninfected group, B19 got transmitted through infected / IgM-positive donor units.
doi:10.4103/0973-6247.83239
PMCID: PMC3159243  PMID: 21897592
B19; blood transfusion; parvovirus; seroconversion; thalassemia
8.  Blood Transfusion Transmitted Infections in Multiple Blood Transfused Patients of Beta Thalassaemia 
Transfusion Transmitted Infection (TTI) continue to be a problem in many parts of world and multi-transfused patients of beta thalassaemia major are at a particularly increased risk of TTI. This study is aimed to estimate the prevalence of blood TTI in multiple blood transfused patients of beta thalassaemia major. Cross-sectional study of 200 multi-transfused patients of beta thalassaemia major, who were interviewed using a structured questionnaire and history was taken regarding sero-status of HIV (Human Immunodeficiency Virus), HBV (Hepatitis B Virus), HCV (Hepatitis C Virus) infection from their case papers. This study was conducted at the department of Pathology, M.P. Shah medical college, Jamnagar and Thalassemia ward, G.G. Hospital, Jamnagar (Gujarat, India) from March to May 2010. Out of 200 multiple blood transfused patients 7% patients were infected with TTI. Total 9 male patients and 5 female patients were infected with TTI. The seroreactivity for HIV was 3% (06/200); 1% (02/200) were males and 2% (04/200) were females. The seroreactivity for HBV was 2% (04/200) all were males. The seroreactivity for HCV was 2% (04/200); 1.5% (03/200) were males and 0.5% (01/200) was female. HIV, HBV, HCV infections are most prevalent TTI among multiple blood transfused patients of beta thalassemia major, and remains a major health problem for these patients.
doi:10.1007/s12288-011-0057-3
PMCID: PMC3136674  PMID: 22654294
Transfusion transmitted infection; Multiple blood transfused patients of beta thalassemia major; Human immunodeficiency virus; Hepatitis B virus; Hepatitis C virus
9.  Hepatitis C virus in sickle cell disease. 
PURPOSE: To determine the prevalence of hepatitis C virus antibodies (anti-HCV) in patients with sickle cell disease. PATIENTS AND METHODS: Between 1983 and 2001, 150 patients from the Howard University Hospital Center for Sickle Cell Disease were screened for HCV antibody (52% women, 48% men, mean age 34 years). Frozen serum samples from 56 adult sickle cell patients who had participated in previous surveys (1983-92) of HIV and HTLV-1 serology and who were tested in 1992 for anti-HCV antibody--when commercial ELISA test (Ortho) became available--were included in this paper. Of the 150 patients in the study, 132 had sickle cell anemia genotype (SS), 15 had sickle cell hemoglobin-C disease (SC) and three had sickle beta thalassemia. Clinical charts were reviewed for history of blood transfusion, IV drug abuse, homosexuality, tattooing, iron overload, and alcohol abuse. RESULTS: Antibodies to HCV were detected in 53 patients (35.3%). Of the 55 patients who had frozen serum samples tested in 1992, 32 (58%) were reactive for anti-HCV, while only 21 of the 95 patients (22%) tested after 1992 were positive for HCV antibodies (P<0.001). Thirty-nine of 77 patients (51%) who received more than 10 units of packed red blood cells were positive for HCV antibody, and only 14 of 61 patients (23%) who received less than 10 units of packed red blood cells transfusion were positive for HCV antibodies (P<0.001). None of the 12 patients who never received transfusion were positive for HCV antibody. In the 53 anti-HCV positive patients, the mean alanine amino-transferase (ALT) value was 98- and 81 U/L, respectively, for males and females. These values were normal for the HCV-antibody negative patients. The aspartate amino-transferase (AST) and the total bilirubin were also higher in the anti-HCV positive patients compared to patients in the anti-HCV negative group. Forty-four patients (57.1%) who were transfused more than 10 units developed iron overload defined by a serum ferritin level higher than 1,000 ng/ml. A total of 20 of the patients with iron overload underwent liver biopsies. Seven of these 20 patients (35%) were HCV positive. These patients often had more severe liver disease and higher degree of iron deposition. CONCLUSION: The prevalence of HCV antibody and iron overload is directly related to the number of blood transfusions in patients with sickle cell disease. The prevalence of HCV infection has decreased significantly, since blood donor screening for HCV became available. Chronic HCV infection and iron overload place sickle cell patients at risk for significant liver disease.
PMCID: PMC2594496  PMID: 14620705
10.  Possible Correlation of Transfusion Transmitted Diseases with Rh type and ABO Blood Group System 
Background: Screening of blood is mandatory for transfusion transmitted diseases and is routinely done in the blood banks. As blood is the major source transmission of hepatitis B, hepatitis C, human immunodeficiency virus & many other diseases the hazards can be minimised by effective donor selection and screening.
Aim: To find out the correlation between the transfusion transmitted diseases and blood groups and the seroprevalence of HIV, HBV, HCV & syphilis among the apparently healthy human blood donors.
Study, Setting & Design: This retrospective study was conducted at the blood bank of a tertiary health care teaching centre for a period of four years.
Material and Methods: All voluntary and replacement donors reporting to the blood bank were screened for HIV-1 & 2, HBsAg, HCV and Syphilis. Anti–HIV -1 & 2, HBsAg & anti - HCV was tested using the appropriate Enzyme–linked immunosorbent assay (ELISA) technique using micro–elisa kit supplied by J.Mitra & Co.Ltd. The seropositive samples were again tested on ELISA kits of RFCL &/or BIORAD for further confirmation & ruling out any false positive or false negative results. The rapid plasma reagain (RPR) test was used for estimation of syphilis infection.
Statistical Analysis: The data entry was carried out using Microsoft office excel worksheet and was analysed by percentage and comparison.
Results: Total of 6000 donors were screened which included voluntary and replacement donors. Seroprevalence of HIV (0.1833 %), HCV (1.28%), HBsAg (1.5833 %) and syphilis (0.4333 %) was detected. In the study done it was also noted - that the NEGATIVE blood groups were more prone to TTIs. Blood group A negative was more prone to TTIs with HIV, HBsAg and VDRL while blood group B negative was more affected by HCV.
Conclusion: Seroprevalence of these infections shows that routine screening is a must for blood and blood product safe transfusion.
Do negative blood groups predispose to TTIs? A finding which makes us think….
doi:10.7860/JCDR/2013/6002.3360
PMCID: PMC3809639  PMID: 24179900
Blood donors; Seroprevalence; Transfusion transmitted diseases; Human immunodeficiency virus; Hepatitis C; Hepatitis B surface antigen
11.  Treponema pallidum hemagglutination assay seroreactivity among healthy Indian donors and its association with other transfusion transmitted diseases 
Background:
The aim of the present study was to determine the prevalence of syphilis infection by Treponema pallidum hemagglutination assay (TPHA) among blood donors in Delhi and to study their correlation with other markers of transfusion transmitted infections such as hepatitis C virus (HCV), human immunodeficiency virus (HIV) and hepatitis B surface antigen (HBsAg) so as to establish the utility of TPHA over and above venereal diseases research laboratory test (VDRL), not only as a marker for testing T. pallidum infection, but also as a marker of high risk behavior.
Materials and Methods:
This prospective study was carried out in the Regional Blood Transfusion Centre, Lady Hardinge Medical College and associated Sucheta Kriplani Hospital, New Delhi for a period of 2 years. Donated blood was screened for TPHA seroreactivity along with screening for anti HIV I and II, anti-HCV, HBsAg by third generation enzyme-linked immunosorbent assay test. A total of 8082 serum samples of blood donors were collected from healthy blood donors in our blood bank. They were classified into two groups- test group and control group based on TPHA positivity. The co-occurrence of HBsAg, HIV and HCV infection were determined in TPHA positive blood donors (test group) in comparison with TPHA negative blood donors (control group).
Results:
We found the TPHA seroreactivity to be 4.4% in Delhi's blood donors. Nearly 8.2% (663/8082) of the donated blood had serological evidence of infection by at least one pathogen (syphilis/HIV/hepatitis B virus/HCV) and 6.63% (44/663) donors with positive serology had multiple infections (two or more). Quadruple infection was seen in one donor, triple infection was seen in three donors and double infection was seen in 40 donors. Prevalence of HIV seroreactivity was found to be statistically significant and HCV seroreactivity statistically insignificant in TPHA positive group in comparison to TPHA negative group.
Discussion:
In our study, the TPHA seropositivity correlated with higher HIV and HCV seropositivity and the same correlation has been observed by several other studies also. In view of these observations, we propose that testing for syphilis by more sensitive and specific treponemal markers like TPHA rather than VDRL, rapid plasma reagin tests; as TPHA also has the added advantage of picking up all the high risk donors, whereas, VDRL picks up only currently infected donors. Moreover, TPHA should be continued as a marker of high risk behavior especially in high prevalence areas like India where we don’t have universal access to markers like nucleic acid amplification technique.
doi:10.4103/0973-6247.137447
PMCID: PMC4140052  PMID: 25161350
Syphilis; Treponema pallidum hemagglutination assay; transfusion transmitted infections; Co-infection
12.  Prevalence of Anti HCV Infection in Patients with Beta-Thalassemia in Isfahan-Iran 
Objectives:
Hepatitis C virus (HCV) is the major cause of post-transfusion hepatitis infection (PTH). Patients with thalassemia major are at high risk of hepatitis C due to the blood transfusion from donors infected by HCV. The aim of this study was to detect the prevalence of anti-HCV antibodies and risk factors in multitransfused thalassemic patients in Isfahan-Iran to establish more preventive strategies.
Methods:
This study was conducted to assess the patients with beta-thalassemia in Isfahan hospitals during 1996-2011 for HCV infection. A structured interview questionnaire was developed by the trained researcher to collect the demographic and risk factors. Statistical analysis was done by Chi-square test, Mann-Withney and multiple logistic regressions using SPSS software, version 15.
Results:
466 patients with major thalassemia participated in this study. The mean age of patients was 17.46 ± 8.3. Two hundred and seventy (58.3%) and 193 (41.7%) of participants were male and female, respectively. The prevalence of HCV was estimated 8% among thalassemia patients. History of surgery, history of dental procedure, number of units transfused per month, number of transfusion per month and duration of transfusion had significant association with HCV seropositivity in univariate analysis. There were no statistical significant risk factors for HCV seropositivity in multiple logistic regression models.
Conclusions:
Our findings revealed that blood transfusion was the main risk factors for HCV infection among beta-thalassemic patients. Therefore, more blood donor screening programs and effective screening techniques are needed to prevent transmission of HCV infection among beta-thalassemic patients.
PMCID: PMC3399295  PMID: 22826753
Beta-thalassemia; HCV infection; Iran
13.  Determination of Hepatitis C Genotypes and the Viral Titer Distribution in Children and Adolescents with Major Thalassemia 
Iranian Journal of Pediatrics  2010;20(1):75-81.
Objective
Hepatitis C virus (HCV) is an etiological agent responsible for occurrence of post-transfusion hepatitis in thalassemic patients. This study identified hepatitis C genotypes in pediatric and adolescent thalassemic patients and their correlation with age, blood transfusion, HCV RNA viral titer and liver function.
Methods
This study considers cross-sectional data from the Center for Thalassemia in Zahedan (Iran) carried out between August 2005 and September 2007. Twenty multitransfused patients suffering from β-thalassemia major and chronic HCV infection (13 males, 7 females) were included in the study. Patients were considered eligible for the study if they were seropositive for HCV RNA polymerase chain reaction (PCR) before initiation of evaluation. Blood sample was taken for HCV genotype and viral titer as well as biochemical markers. Type specific primer and real-time RT-PCR HCV were used for determination of viral genotype and HCV-RNA titer.
Findings
There was a significant positive correlation between serum HCV RNA titer and genotypes (P<0001). Serum HCV RNA levels were found higher in genotype 3a than in others. The most prevalent genotype in thalassemic patients was genotype 3a (40%) followed by 1b (25%), unclassified (20%) and la (15%). There was no meaningful relationship between genotype, Alanine aminotranferease, ferritin and alkaline phosphatase. Age, serum HCV RNA titer and number of transfusions were the only significant factors associated with genotypes (P<015, P<0.0001 and P<0.001 respectively).
Conclusion
This study showed that HCV genotype and viral titer are related to the number of blood transfusions received by thalassemic patients. Screening donated blood in blood banks would prevent the occurrence of hepatitis C in this high-risk group.
PMCID: PMC3445996  PMID: 23056686
Hepatitis C; Virus Titer; Viral Load; Liver Function Tests; Thalassemia; Iran
14.  Seroprevalence of human immunodeficiency virus, hepatitis B and C viruses and syphilis among blood donors in Koudougou (Burkina Faso) in 2009 
Blood Transfusion  2011;9(4):419-424.
Background
The high prevalence of numerous transfusion-transmitted infectious diseases such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis in sub-Saharan Africa affects the safety of blood for recipients. This study was undertaken with the aim of determining the seroprevalence of HIV, HCV, HBV, syphilis and socio-demographic risk factors associated with blood donation in a new regional blood transfusion centre in Burkina Faso.
Material and methods
Sera samples were screened for hepatitis B surface antigen (HBsAg), antibodies to HCV, HIV types 1 and 2 and to Treponema pallidum using enzyme-linked immunosorbent assays and Rapid Plasma Reagin test (RPR) respectively. All the reactive samples for HIV, HBsAg, and HCV were confirmed using a second enzyme-linked immunosorbent assays. Antibodies to Treponema pallidum were confirmed with a Treponema pallidum haemagglutination test (TPHA).
Results
From the total of 4,520 blood donors in 2009, 1,348 (29.82%) were infected with at least one pathogen and 149 (3.30%) had serological evidence of multiple infections. The overall seroprevalence rate of HIV, HBV, HCV and syphilis was 2.21%, 14.96%, 8.69% and 3.96%, respectively. Among blood donors with multiples infections, the most common dual or triple combinations were HBsAg-HCV (1.39%), HBsAg-syphilis (0.66%) and HBsAg-HCV-syphilis (0.11%). The highest prevalences of HBsAg and HIV were found among blood donors from rural areas and in the age groups of 20–29 years and >40 years old, respectively.
Conclusion
HBV and HCV remain the greatest threats to blood safety in Burkina Faso. Strict selection and retention of voluntary, non-remunerated low-risk blood donors are recommended to improve blood safety in the regional blood transfusion centre of Koudougou.
doi:10.2450/2011.0112-10
PMCID: PMC3200412  PMID: 21839011
transfusion; blood donors; HBV; HCV; Burkina Faso
15.  Prevalence of Serological Markers for Hepatitis B and C Viruses in Brazilian Blood Donors, and Incidence and Residual Risk of Transfusion-Transmission of Hepatitis C Virus 
Transfusion  2012;53(4):827-834.
Background
We evaluate the current prevalence of serological markers for HBV and HCV in blood donors and estimated HCV incidence and residual transfusion-transmitted risk at three large Brazilian blood centers.
Material and Methods
Data on whole blood and platelet donations were collected from January through December 2007 and analyzed by center, donor type (replacement vs. community), age, sex, donation status (first-time vs. repeat), and serological results for HBsAg, anti-HBc and anti-HCV. HBV (HBsAg+/anti-HBc+) and HCV (anti-HCV) prevalence rates were calculated for all first time donations. HCV incidence was derived including inter-donation intervals that preceded first repeat donations given during the study and HCV residual risk was estimated for transfusions derived from repeat donors.
Results
There were 307,354 donations from January through December 2007. Overall prevalence of concordant HBsAg and anti-HBc reactivity was 289 per 100,000 donations and of anti-HCV confirmed reactivity 191 per 100,000 donations. There were significant associations between older age and hepatitis markers, especially for HCV. HCV incidence was 3.11 (95% CI 0.77-7.03) per 100,000 person-years, and residual risk of HCV window-phase infections was estimated at 5.0 per million units transfused.
Conclusion
Improvement in blood donor selection, socioeconomic conditions and preventive measures, implemented over time, may have helped to decrease prevalence of hepatitis B and C viruses, relative to previous reports. Incidence and residual risk of HCV are also diminishing. Ongoing monitoring of hepatitis B and C viral markers among Brazilian blood donors should help guide improved recruitment procedures, donor selection, laboratory screening methods and counseling strategies.
doi:10.1111/j.1537-2995.2012.03840.x
PMCID: PMC3499633  PMID: 22882510
Blood donors; Brazil; Residual Risk; Hepatitis B; Hepatitis C; Prevalence; Incidence
16.  Hepatitis B and/or C co-infection in HIV infected patients: A study in a tertiary care centre from south India 
Background & objectives:
Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in human immunodeficiency virus (HIV) infected individuals results in increased hepatic complications. We undertook this study to evaluate the presence of HBV and HCV in HIV infected individuals attending a tertiary care centre in southern India.
Methods:
A total of 120 cases with HIV infection and 120 healthy adult control subjects were included in the study. Samples were tested for hepatitis B surface antigen (HBsAg) and anti-HCV antibodies by enzyme linked immunosorbent assay (ELISA) method. HBsAg and anti-HCV positive serum samples were further tested for the presence of hepatitis B e antigen (HBeAg), anti-HBe antibodies, HBV-DNA and HCV-RNA.
Results:
The most common mode of transmission was sexual promiscuity (79%), followed by spouse positivity (15%) and history of blood transfusion (6%). HBsAg and anti-HCV were positive in 18 (15%) and 10 (8.3%) HIV infected patients; the corresponding figures in healthy controls being 2 (1.6%) 0 (0%) (P<0.0001). Among HIV infected patients, presence of HBeAg and anti-HBe antibodies was seen in 33.3 and 55.5 per cent, respectively; both HBeAg and anti-HBe antibodies were negative in 11.1 per cent. HBV DNA and HCV RNA were positive in 10 of 18 and in all anti-HCV positive samples. Triple infection with HBV, HCV and HIV was seen in three patients. CD4+ T-lymphocyte count less than 200/μl was seen in 22 of 28 co-infected cases.
Interpretation & conclusions:
The findings of our study showed presence of HBV (15%) and HCV (8.3%) co-infections in HIV positive patients which was higher than that seen in HIV negative controls. Co-infection with HBV and HCV is a common problem in HIV infected patients in India. Hence, all HIV patients need to be routinely tested for markers of HBV and HCV infection.
PMCID: PMC3978987  PMID: 24521641
Co-infection; hepatitis B virus; hepatitis C virus; human immunodeficiency virus
17.  Prevalence of Antibodies to Hepatitis C Virus in Voluntary Blood Donors: Are Women Better Donors? 
Background: Hepatitis C virus (HCV) is transmitted by blood and blood products and it causes a major proportion of transfusion transmitted hepatitis. It can lead to chronic liver disease which has great morbidity and mortality. HCV is responsible for more deaths than Human immunodeficiency virus (HIV). As no vaccine is available and as the treatment is costly and lengthy, with a poor success rate, donor screening remains a very important means of primary prevention of HCV transmission.
Aims and Objectives: This study was conducted to know the prevalence of anti-HCV in healthy voluntary blood donors (VBD) in a semi-urban region of western Maharashtra, India with a special focus on female donors.
Settings and Design: This was an unlinked, anonymous, retrospective study.
Materials and Methods: During January 2006 to December 2012, sera of 17976 VBD, which comprised of 16972 (94.41%) males and 1004 (5.59%) females, were tested for presence of anti-HCV antibody (anti-HCV) by using a 3rd generation ELISA test. Data was statistically analyzed by using Chi-Square for linear trends (Extended Mantel-Haenszel test). - 0.72732.
Results and Conclusion: Thirty six donors (0.2%) were positive for anti-HCV. Seroprevalence in males was 0.21%, while that in females was 0%. The positivity of anti-HCV remained stable over the tenure of this study (Chi-Square for linear trends - 0.72732). This region has a lower prevalence of anti-HCV as compared those seen in other states of India. Zero prevalence in women indicated that encouraging women to undergo blood donations would still reduce the transmission of HCV. Detection can be improved by doing better tests like HCV RNA detection and further prevention of HCV transmission can be enhanced.
doi:10.7860/JCDR/2014/7575.4295
PMCID: PMC4064908  PMID: 24959444
Voluntary blood donors; Blood transfusion; Hepatitis C; HCV; Anti-HCV
18.  The Prevalence of Transfusion Transmitted Infections in ABO Blood Groups and Rh Type System 
Hematology Reports  2014;6(4):5602.
Screening of blood and blood products is important to reduce the risk of transfusion transmitted infections (TTIs). The transfusion of unscreened or inadequately screened blood and blood products are the major source of TTIs. The aim of this paper is to find out the prevalence of TTIs in ABO blood groups and Rh type system. A total of 4128 blood donors were screened from January 2010 to April 2014. Serological tests were performed for hepatitis B surface antigen (HBsAg), anti hepatitis C virus (Anti-HCV), anti HIV-1 and 2, venereal disease research Laboratory test (VDRL) and malaria parasite (MP) antigen. In seroreactive donors, HBsAg, Anti-HCV, VDRL, MP antigen and anti HIV were positive in 40 cases, 26 cases, 19 cases, 6 cases and 2 cases, respectively. Highest percentage of HBsAg, Anti HCV, VDRL, MP antigen and anti HIV was observed in blood group A negative (2/50), O negative (1/66), B negative (1/91), AB positive (2/377) blood group respectively. In the present study, the total number of Rhnegative donors is lower when compared to Rh-positive blood donors, but Rh-negative blood donors show higher percentages of seroreactivity for TTIs. Larger scale studies at molecular level are required to improve the knowledge of this aspect.
doi:10.4081/hr.2014.5602
PMCID: PMC4274480  PMID: 25568761
transfusion transmitted infections; blood products; ABO blood groups; Rh type system; India
19.  Seroprevalence of HBV, HCV & HIV Co-Infection and Risk Factors Analysis in Tripoli-Libya 
PLoS ONE  2014;9(6):e98793.
Background
In 1998 Libya experienced a major outbreak of multiple blood borne viral hepatitis and HIV infections. Since then, no studies have been done on the epidemic features and risk factors of HBV, HCV, HIV and co-infection among the general population.
Methods
A prospective study was carried out using a multi-centre clustering method to collect samples from the general population. The participants were interviewed, and relevant information was collected, including socio-demographic, ethnic, and geographic variables. This information was correlated with the risk factors involved in the transmission of HBV, HCV and HIV. Blood samples were collected and the sera were tested for HBsAg, anti-HCV and anti-HIV using enzyme immunoassay.
Results
A total of 9,170 participants from the nine districts of Tripoli were enrolled. The average prevalence of HBsAg was 3.7%, anti-HCV 0.9%, anti-HIV 0.15% and co-infection 0.02%. The prevalence varied from one district to another. HBV was more prevalent among those aged over 50 years and was associated with family history. Anti-HCV and anti-HIV were more prevalent among those aged 20–40 years. Intravenous drug use and blood transfusion were the main risk factors for HCV and HIV infection.
Conclusion
HBV, HCV, HIV and co-infection are relatively common in Libya. High prevalence was associated with geographic, ethnic and socioeconomic variability within the community. HCV and HIV infections among the younger age groups are becoming an alarming issue. Regulations and health care education need to be implemented and longer term follow-up should be planned.
doi:10.1371/journal.pone.0098793
PMCID: PMC4060988  PMID: 24936655
20.  Hepatitis G virus infection in Egyptian children with chronic renal failure (single centre study) 
Background
Hepatitis G virus (HGV) is an RNA virus. It is mainly transmitted through exposure to contaminated blood although other routes may also exist. Patients with chronic renal failure (CRF) are at high risk of acquiring HGV because they require frequent blood transfusions. Ongoing HGV infection can be only diagnosed by demonstrating viremia in patient sample by reverse transcriptase (RT) PCR. Antibodies to the envelop protein E2 (anti E2) of HGV is an indicator of virus clearance and testify past HGV contact. This cross sectional study was done to assess the frequency of HGV exposure (ongoing and past infection) in Egyptian children with CRF and to study the possible risk factors of infection.
Methods
This study included 100 children with CRF [34 on regular haemodialysis (HD) and 66 before the start of dialysis (predialysis)]. All patients sera were tested for HGV RNA by RT-PCR, anti E2, hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (HBcAB). Twenty five healthy children of matched age & sex were used as controls.
Results
HGV RNA was positive in 9 (26.5%) of HD and 9 (13.6%) of predialysis children. Anti E2 was positive in 14 (41.2%) of HD and 19 (28.8%) of predialysis children.
In comparison to controls; CRF (n = 100); HD and predialysis children had significantly higher prevalence of anti E2 [4% VS 33% for all CRF cases; (p = 0.002)& 41.2% (p = 0.002) and 28.8% (p = 0.01); for HD and predialysis groups; respectively]. HGV RNA was significantly more prevalent only in HD children in comparison to controls (p = 0.03). HD and predialysis children did not have significant difference in the prevalence of HGV RNA (p = 0.16) or anti E2 (p = 0.26).
HGV exposure was not correlated with positivity of anti HCV (p = 0.32), HCV RNA (0.09), HBsAg/HBcAB (p = 1), age (p = 0.06), or gender (p = 0.83). It was significantly correlated with duration of the disease (p < 0.001). Ongoing HGV infection was significantly more prevalent with frequent blood transfusion (p < 0.001). There were no significant differences in serum levels of ALT (p = 0.09), total bilirubin (p = 0.1) and albumin (p = 0.06) in children with ongoing infection in comparison to healthy controls.
Conclusions
The frequency of HGV exposure in Egyptian children with CRF appears to be high and is mainly related to frequent blood transfusions and longer disease duration. HGV infection in these children is not associated with significant changes in hepatic biochemical parameters.
doi:10.1186/1476-0711-8-36
PMCID: PMC2804678  PMID: 20015406
21.  Hepatitis B and C infection in haemodialysis patients in Libya: prevalence, incidence and risk factors 
BMC Infectious Diseases  2012;12:265.
Background
Patients receiving maintenance haemodialysis (HD) are at higher risk for acquiring Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infections than the general population. Strict infection control measures are essential to prevent nosocomial transmission. We aimed to investigate the incidence and prevalence of HBV and HCV infection in the HD population of Libya as well as risk factors for infection.
Methods
All adult patients receiving maintenance HD (n=2382) in Libyan dialysis centres (n=39) were studied between May 2009 and October 2010. Testing for Hepatitis B surface antigen (HBsAg) and anti-HCV antibodies was performed at initiation of dialysis and every 3–6 months thereafter. Patients who were sero-negative for HBV and HCV (n=1160) were followed up for 1 year to detect sero-conversions.
Results
Participant median age was 49 years and 58% were male. 831 patients (34.9%) were sero-positive for HBV and/or HCV (anti-HCV positive 31.1%; HBsAg positive 2.6%; both positive 1.2%). Of the sero-positive patients 4.7% were known to be infected before the initiation of HD. The prevalence of HBV±HCV infection varied widely between HD centres from 0% to 75.9%. Sero-positive patients were younger, had longer time on dialysis and more previous blood transfusions. Prospective follow-up revealed an incidence of sero-conversion of 7.7% during 1 year (7.1% HCV; 0.6% HBV). Wide variation in rates of newly acquired infections was observed between dialysis centres. All new HBV cases were referred from centres already treating HBV infected patients. New HCV infections were reported in most centres but the rate of HCV sero-conversion varied widely from 1.5% to 31%. Duration of dialysis, history of previous renal transplant and history of receiving HD in another centre in Libya were significantly associated with sero-conversion.
Conclusion
Patients on maintenance HD in Libya have a high incidence and prevalence of HCV infection and lower rates of HBV infection. The factors associated with HBV and HCV infection are highly suggestive of nosocomial transmission within HD units. Urgent action is required to improve infection control measures in HD centres and to reduce dependence on blood transfusions for the treatment of anaemia.
doi:10.1186/1471-2334-12-265
PMCID: PMC3507892  PMID: 23082935
Haemodialysis; Hepatitis B; Hepatitis C; Incidence; Libya; Nosocomial infection; Prevalence
22.  Patient-to-Patient Transmission of Hepatitis C at Iranian Thalassemia Centers Shown by Genetic Characterization of Viral Strains 
Hepatitis Monthly  2013;13(1):e7699.
Background
Hepatitis C is prevalent among thalassemia patients in Iran. It is mainly transfusion mediated, in particular among patients treated before 1996 when blood screening was introduced.
Objectives
The current study aimed to investigate why patients still seroconvert to anti-HCV in Iranian thalassemia centers.
Patients and Methods
During 2006-2007 sera were sampled from 217 anti-HCV positive thalassemia patients at nine thalassemia centers in Tehran and Amol city, where 34 (16%) patients had been infected after 1996. The HCV subtype could be determined by sequencing and phylogenetic analysis of partial NS5B and/or 5׳NCR-core region in 130 strains.
Results
1a (53%) was predominant followed by 3a (30%), 1b (15%), and one strain each of 2k, 3k and 4a. Phylogenetic analysis revealed 19 clades with up to five strains diverging with less than six nucleotides from each other within subtypes 1a and 3a. Strains in seven clades were from nine patients infected between 1999 and 2005 and similar to strains from eight patients infected before 1996, indicating ongoing transmission at the centers. Further epidemiological investigation revealed that 28 patients infected with strains within the same clade had frequently been transfused at the same shift sitting on the same bed. An additional eight patients with related strains had frequently been transfused simultaneously in the same room.
Conclusions
The results suggest nosocomial transmission at these thalassemia centers both before and after the introduction of blood screening. Further training of staff and strict adherence to preventive measures are thus essential to reduce the incidence of new HCV infections.
doi:10.5812/hepatmon.7699
PMCID: PMC3622054  PMID: 23585766
Hepatitis C; Thalassemia; Iran
23.  Prevalence and Predictors of Hepatitis B Virus Co-infection in a United States Cohort of Hepatitis C Virus-infected Patients 
Hepatology (Baltimore, Md.)  2013;58(2):538-545.
Background and Aim
There is sparse epidemiologic data on co-infection of hepatitis B (HBV) and hepatitis C (HCV) in the United States. Therefore, the aim of this study was to determine the prevalence and predictors of HBV co-infection in a large United States population of HCV patients.
Methods
We used the National Veterans Affairs HCV Clinical Case Registry to identify patients tested for HCV during 1997–2005. Patients were categorized based on HCV exposure (any two +HCV tests or one test with a diagnostic code), HCV infection (+RNA or genotype), HBV exposure (any +HBV test, excluding +HBsAb only) and HBV infection (+HBsAg, HBV DNA, or HBeAg). The prevalence of HBV exposure among patients with HCV exposure and that of HBV infection among patients with HCV infection were determined. Multivariable logistic regression evaluated potential demographic and clinical predictors of HBV co-infection.
Results
Among 168,239 patients with HCV exposure, 58,415 patients had HBV exposure for a prevalence of 34.7% (95% CI 34.5–35.0). Among 102,971 patients with HCV infection, 1,431 patients had HBV co-infection for a prevalence of 1.4% (95% CI 1.3–1.5). Independent associations with HBV co-infection compared with HCV mono-infection were age ≤ 50 years, male sex, positive HIV status, history of hemophilia, sickle cell anemia or thalassemia, history of blood transfusion, cocaine and other drug use; there was decreased risk in patients of Hispanic ethnicity.
Conclusions
This is the largest cohort study in the United States on the prevalence of HBV co-infection in HCV patients. Among veterans with HCV, exposure to HBV is common (~35%), but HBV co-infection is relatively low (1.4%). Several possible risk factors were identified.
doi:10.1002/hep.26400
PMCID: PMC3729715  PMID: 23505059
Epidemiology; Risk factors; HBV; HCV; Viral hepatitis
24.  Evaluation of the Prevalence of Hepatitis B, Hepatitis C, and HIV in Inmates with Drug-Related Convictions in Birjand, Iran in 2008 
Hepatitis Monthly  2010;10(1):26-30.
Background and Aims
Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) are common infections among prisoners. Addicted prisoners are at a higher risk than the normal population for contracting these diseases. Many studies have reported higher prevalence rates of HBV, HCV, and HIV in prisoners. Because of this problem, this study was conducted to evaluate the serologic prevalence of these three diseases in prisoners convicted of drug-related crimes.
Methods
A descriptive cross-sectional study was conducted on a random sample of prisoners with drug charges who were inmates in a prison in Birjand, Iran. Information was collected via questionnaire after obtaining prisoners’ informed consent and blood samples were tested for hepatitis B surface antigen (HBsAg), antibodies to HCV (anti-HCV), and antibodies to HIV (anti-HIV). The results were analyzed by chi-square tests.
Results
In this study, 358 prisoners were selected. 80.2% of prisoners were male, and 19.8% were female. The average age was 34.7±12 years. 39.1% were addicted to drugs, 54.2% were smokers, and 19.3% had tattoos. 8.4% had had extramarital intercourse, and 16.8% had had a sexually transmitted disease (STD) in past. HBsAg, anti-HCV, and anti- HIV prevalence in these samples were 6.1%, 8.1%, and 0%, respectively.The prevalence rate of HBV in the addicted prisoners was 4.3%, and the rate in non-addicted prisoners was 7.3% (P = 0.24).The prevalence of HCV in addicted prisoners was 15.7%, and the prevalence in non-addicted prisoners was 3.2%; this difference was significant (P < 0.001).Furthermore, a significant difference between the prevalence of HBV and extramarital intercourse was noted (P < 0.005).A significant difference between HCV and transfusion, history of STDs, addiction, and tattooing was noted.
Conclusions
The survey showed that HCV, HBV, and HIV prevalence rates in prisoners were 8.1%, 6.1%, 0%, respectively. The prevalence rates of HCV and HBV in addicted prisoners were 15.7% and 4.3 %, respectively. Studies performed in Iran and other countries have shown that the prevalence rates of HBV, HCV, and HIV in addicted prisoners were higher than the rates in non-addicted prisoners. These results indicate that HBV, HCV, and HIV are significant problems in prisons, and efforts to reduce the risk of these infections, such as education and vaccination, should be considered.
PMCID: PMC3270341  PMID: 22308122
HBV; HCV; HIV; Prisoner; Drug-Related Crimes
25.  The Global Spread of Hepatitis C Virus 1a and 1b: A Phylodynamic and Phylogeographic Analysis 
PLoS Medicine  2009;6(12):e1000198.
Using phylodynamic and phylogeographic methods, Angelos Hatzakis and colleagues find that the global spread of Hepatitis C virus coincided with widespread use of transfused blood and with the expansion of intravenous drug use.
Background
Hepatitis C virus (HCV) is estimated to affect 130–180 million people worldwide. Although its origin is unknown, patterns of viral diversity suggest that HCV genotype 1 probably originated from West Africa. Previous attempts to estimate the spatiotemporal parameters of the virus, both globally and regionally, have suggested that epidemic HCV transmission began in 1900 and grew steadily until the late 1980s. However, epidemiological data suggest that the expansion of HCV may have occurred after the Second World War. The aim of our study was to elucidate the timescale and route of the global spread of HCV.
Methods and Findings
We show that the rarely sequenced HCV region (E2P7NS2) is more informative for molecular epidemiology studies than the more commonly used NS5B region. We applied phylodynamic methods to a substantial set of new E2P7NS2 and NS5B sequences, together with all available global HCV sequences with information in both of these genomic regions, in order to estimate the timescale and nature of the global expansion of the most prevalent HCV subtypes, 1a and 1b. We showed that transmission of subtypes 1a and 1b “exploded” between 1940 and 1980, with the spread of 1b preceding that of 1a by at least 16 y (95% confidence interval 15–17). Phylogeographic analysis of all available NS5B sequences suggests that HCV subtypes 1a and 1b disseminated from the developed world to the developing countries.
Conclusions
The evolutionary rate of HCV appears faster than previously suggested. The global spread of HCV coincided with the widespread use of transfused blood and blood products and with the expansion of intravenous drug use but slowed prior to the wide implementation of anti-HCV screening. Differences in the transmission routes associated with subtypes 1a and 1b provide an explanation of the relatively earlier expansion of 1b. Our data show that the most plausible route of the HCV dispersal was from developed countries to the developing world.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 150 million people (3% of the world's population) harbor long-term (chronic) infections with the hepatitis C virus (HCV) and about 3–4 million people become infected with this virus every year. HCV—a leading cause of chronic hepatitis (inflammation of the liver)—is spread through contact with infected blood. Transmission routes include medical procedures (for example, transfusions with unscreened blood) and needle-sharing among intravenous drug users. This second transmission route is the most common one in developed countries where blood is now routinely screened before being used in transfusions. HCV infection can cause a short-lived illness characterized by tiredness and jaundice (yellow skin and eyes), but most newly infected people progress to a symptom-free, chronic infection that can eventually cause liver cirrhosis (scarring) and liver cancer. HCV infections can be treated with a combination of two expensive drugs called interferon and ribavirin, but these drugs are ineffective in many patients.
Why Was This Study Done?
Noone knows for sure where HCV originated although there is some evidence that it appeared first in West Africa or Southeast Asia. It is also unclear when the current HCV epidemic began. In this study, the researchers try to elucidate both the timescale and route of the global spread of the HCV epidemic by analyzing the genome sequence of HCV samples collected at different times and places. HCV is a ribonucleic acid (RNA) virus. That is, it stores the information it needs to replicate itself—its genome—as a series of “ribonucleotides.” Like other RNA viruses, the HCV genome continually accumulates small changes (mutations) and, over time, HCV has evolved into several different “genotypes,” each of which has several distinct subtypes. Furthermore, the viruses within a single subtype have subtly different genomes. By analyzing this viral diversity using complex “phylodynamic” and “phylogeographic” methods, scientists can build up a picture of how HCV has evolved in populations and how it has spread to reach its current geographical distribution.
What Did the Researchers Do and Find?
By examining the genomes of HCV samples collected between 1994 and 2006 at the Athens University Medical School (Greece), the researchers first defined a variable region of HCV called E2P7NS2 that is more informative for phylodynamic studies than the NS5B region that has been used in previous studies. They then retrieved the sequences of both regions for subtype 1a and 1b samples collected over the past 20–30 years in the Los Alamos HCV sequence database; HCV subtypes 1a and 1b cause 60% of global HCV infections. The researchers' phylodynamic analyses of these globally representative sequences (collected in the USA, Germany, Switzerland, and Greece) indicate that the transmission of HCV subtype 1a occurred at a low rate from 1906 until the 1960s, at which time there was an explosive increase in its transmission rate. Similarly, subtype 1b transmission occurred at a low rate from 1922 until the late 1940s but then increased exponentially. From 1980 onwards, the prevalence of both subtypes stabilized at a high level. The researchers' phylogeographic analyses (which considered 1a and1b NS5B sequences collected in 21 and 29 countries, respectively) suggest that HCV subtypes 1a and 1b may have spread from the developed to the developing world.
What Do These Findings Mean?
These findings indicate that the epidemic of HCV subtype 1b began in the 1940s when the use of transfused blood and blood products became widespread whereas the start of the subtype 1a epidemic coincided with the expansion of injected drug use that occurred in the 1960s. The findings also suggest that the transmission rates of both subtypes may have slowed before the widespread implementation of HCV screening in the early 1990s, possibly because the medical community was aware by then of the general risks associated with blood contamination. Finally, these findings provide new insights into how the HCV epidemic spread around the world and suggest that HCV may be evolving faster than previously thought. However, because this study relied on a small number of samples collected over a short time period, its findings need to be confirmed in larger studies.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000198.
The World Health Organization provides detailed information about hepatitis C and HCV
The US Centers for Disease Control and Prevention provides information on hepatitis C for the public and for health professionals (information is also available in Spanish)
The US National Institute of Diabetes and Digestive and Kidney Diseases provides basic information on hepatitis C (in English and Spanish)
MedlinePlus provides links to further resources on hepatitis C
The Los Alamos HCV database is available
The US National Center for Biotechnology Information provides a science primer on how scientists reconstruct evolutionary pathways from sequence information
doi:10.1371/journal.pmed.1000198
PMCID: PMC2795363  PMID: 20041120

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