Memórias do Instituto Oswaldo Cruz Fundação Oswaldo Cruz, Fiocruz ISSN: 1678-8060 EISSN: 1678-8060 Vol. 97, Num. 7, 2002, pp. 953-957

Mem Inst Oswaldo Cruz, Rio de 
  Janeiro, Vol. 97(7), October 
  2002, pp. 953-957
Prevalence and 
  Genotypes of GB Virus C/Hepatitis G Virus among Blood Donors in Central Brazil 
  
Luciana A Oliveira, Regina MB Martins/+, 
  Megmar AS Carneiro, Sheila A Teles, Simonne A Silva, Divina DP Cardoso, Elisabeth 
  Lampe*, Clara FT Yoshida*
Instituto de Patologia Tropical e 
  Saúde Pública, Universidade Federal de Goiás, Caixa Postal 
  131, 74605-050 Goiânia, GO, Brasil *Departamento de Virologia, Instituto 
  Oswaldo Cruz-Fiocruz, Rio de Janeiro, RJ, Brasil 

  +Corresponding 
  author. Fax: +55-62-202.3066. E-mail: rbringel@terra.com.br 
  
Received 7 March 2002 

  Accepted 12 June 2002
This 
  work received financial support from Conciteg and CNPq. 
Code Number: oc02217 
  
A survey was conducted in a blood 
  donor population of Central Brazil aiming to investigate the prevalence of GB 
  virus C (GBV-C)/hepatitis G virus (HGV) infection and also to analyze the virus 
  genotypes distribution. A total of 241 voluntary blood donors were interviewed 
  at the State Blood Bank in Goiânia, State of Goiás, Brazil. Blood 
  samples were collected and serum samples tested for GBV-C/HGV RNA by polymerase 
  chain reaction. Genotypes were determined by restriction fragment length polymorphism 
  (RFLP) analysis. Seventeen samples were GBV-C/HGV RNA-positive, resulting in 
  a prevalence of 7.1% (95% CI: 4.2-11.1). A significant trend of GBV-C/HGV RNA 
  positivity in relation to age was observed, with the highest prevalence in donors 
  between 29-39 years old. Ten infected individuals were characterized by reporting 
  parenteral (30%), sexual (18%), both (6%) and intrafamiliar (6%) transmission. 
  However, 7 (40%) GBV-C/HGV RNA-positive donors did not mention any potential 
  transmission route. RFLP analysis revealed the presence of genotypes 1 and 2 
  of GBV-C/HGV; more precisely, 10 (58.9%) samples were found belonging to the 
  2b subtype, 4 (23.5%) to the 2a subtype, and 3 (17.6%) to genotype 1. The present 
  data indicate an intermediate endemicity of GBV-C/HGV infection among this blood 
  donor population, and a predominant circulation of genotype 2 (subtype 2b) in 
  Central Brazil. 
Key words: hepatitis G virus - GB 
  virus C - blood donors - Goiânia - Central Brazil 
GB virus C (GBV-C) and hepatitis 
  G virus (HGV) are independent isolates of the same virus which were identified 
  as possible aetiological agent of viral hepatitis in humans (Simons et al. 1995, 
  Linnen et al. 1996). The GBV-C/HGV can cause persistent infection, but its role 
  in causing liver diseases is still uncertain (Bowden 2001). However, some studies 
  showed that infection with GBV-C/HGV can be associated with lower progression 
  of human immunodeficiency virus (HIV) disease in coinfected patients (Lefrère 
  et al. 1999, Yeo et al. 2000, Tillmann et al. 2001, Xiang et al. 2001). 
The GBV-C/HGV genome consists of 
  a single-stranded positive sense RNA of approximately 9.4 kb which has characteristics 
  of a flavivirus-like genome as in the case of the hepatitis C virus (HCV) (Muerhoff 
  et al. 1995), except that unlike HCV, the 5' noncoding region (5' NCR) of GBV-C/HGV 
  is variable, and can be used initially to classify natural isolates into three 
  genotypes. Genotype 1 is frequently found in West Africa, genotype 2 predominates 
  in the USA and Europe, and genotype 3 is commonly observed in parts of Asia 
  (Muerhoff et al. 1996, 1997, Mukaide et al. 1997, Okamoto et al. 1997, Katayama 
  et al. 1998). In addition to this classification, 2 novel genotypes were identified. 
  Genotype 4 was described in Myanmar and Vietnam (Naito et al. 2000), and genotype 
  5 has been found in South Africa (Tucker et al. 1999, Tucker & Smuts 2000). 
  
GBV-C/HGV is transmitted through 
  blood transfusion and blood components (Schmidt et al. 1996, Roth et al. 1997, 
  Heuft et al. 1998). Epidemiological data suggest that this virus is also spread 
  by sexual and vertical transmission (Bourlet et al. 1999, Stark et al. 1999, 
  Wejstål et al. 1999). However, little is known about other modes of transmission 
  that could explain the high prevalence and worldwide distribution of this virus. 
  
In Brazil, high GBV-C/HGV RNA prevalence 
  rates were found in blood donors from Southeast and Northeast regions (Bassit 
  et al. 1997, Lampe et al. 1998a, Goubau et al. 1999, Pinho et al. 1999). As 
  data concerning GBV-C/HGV infection in other Brazilian regions are still rare, 
  we sought to assess the prevalence of GBV-C/HGV RNA in blood donors in Central 
  Brazil and also to investigate the virus genotypes distribution. 
MATERIALS AND METHODS 
Subjects - From June to September 
  2000, a total of 241 voluntary blood donors accepted for blood donation, after 
  clinical evaluation, at the State Blood Bank in Goiânia, State of Goiás 
  (1,000,000 inhabitants), Central Brazil, were invited to take part of this study, 
  and informed consent was obtained from all participants. The study was approved 
  by the Ethical Committee of the Federal University of Goiás. 
A standardized form was used to collect 
  sociodemo-graphic and data as number of previous blood transfusions, acupuncture, 
  tattooing, surgery, intravenous drug use, dental procedure with non-licensed 
  dentist, multiple sex partners, sexually transmitted diseases, and possible 
  household contact with hepatitis. 
Serological tests - Blood 
  samples were collected from all donors and sera were stored at -20ºC. They 
  were screened for hepatitis B surface antigen (HBsAg), hepatitis B core antibody 
  (anti-HBc) and hepatitis C antibody (anti-HCV) by enzyme-linked immunosorbent 
  assays (ELISA) (Abbott Laboratories, USA). All samples were also tested for 
  alanine aminotransferase (ALT) levels by a colorimetric method (Dolles Laboratory, 
  Brazil). 
Detection of GBV-C/HGV RNA 
  - All samples were submitted to RNA extraction, reverse transcription, and a 
  nested polymerase chain reaction (PCR) with primers complementary to the conserved 
  area of the NS5 region of the genome, essentially as described by Lampe et al. 
  (1997). 
GBV-C/HGV genotyping - GBV-C/HGV 
  RNA-positive samples were amplified by PCR using primers complementary to the 
  5' non-coding region (NCR). Genotypes were determined by means of RFLP method 
  (Quarleri et al. 1999). Briefly, amplicons were initially cleaved with Hinf 
  I, and depending on the restriction pattern observed, a second digestion was 
  performed either with Aci I or Aat II. Restriction fragments were 
  resolved in ethidium bromide-stained 3% agarose gels. 
Statistical analysis - Prevalence 
  and 95% confidence intervals (CI) were calculated. Chi-square test, Chi-square 
  for trend test or Fisher's exact test were performed to evaluate the distribution 
  of characteristics associated with GBV-C/HGV infection. Statistical significance 
  was assessed at the 0.05 probability level in all analyses. Statistical evaluations 
  were performed using Epiinfo 6.0 program developed by the Centers for Disease 
  Control and Prevention (Atlanta, GA). 
RESULTS 
The studied population ranged in 
  age from 18 to 60 years (mean ± SD = 30.2 ± 8.5 years). The majority 
  of the blood donors (86.7%) were men. Almost 70% of them earned less than U$ 
  200 per month and also had less than 8 years of schooling. Forty-eight (19.9%) 
  were first-time blood donors and 193 (80.1%) were regular donors. This population 
  consisted of relatives or close friends of hospitalized patients needing blood 
  transfusions. 
As shown in Table 
  I, a prevalence of 7.1% (95% CI: 4.2-11.1) was found for GBV-C/HGV infection. 
  This donor population showed positivity rates of 5% and 0.8% for hepatitis B 
  (anti-HBc) and C (anti-HCV), respectively. All serum samples were negative for 
  HBsAg. 
Analysis of the characteristics of 
  this population showed that only age was significantly associated with GBV-C/HGV 
  infection. This infection reached a peak at an age range from 29 to 39 years 
  old; 13.5% of the blood donors were infected. Moreover, 2.5% of the age group 
  under 28 years and 6.1% of age group over 40 years were GBV-C/HGV RNA- positive 
  (c² for trend = 9.98; p = 0.018). On the other 
  hand, potential transmission routes associated with parenteral (30%), sexual 
  (18%), both (6%) and intrafamiliar (6%) were reported by GBV-C/HGV RNA-positive 
  donors. However, 40% of them did not mention any known source for infection 
  (Table II). GBV-C/HGV RNA-positive 
  individuals ranged in age from 21 to 43 years. All but one were men. The majority 
  of them were regular blood donors. Two of these donors (nos. 5 and 14) were 
  anti-HBc positive. All GBV-C/HGV infected individuals had normal ALT levels. 
  
All 17 GBV-C/HGV RNA-positive samples 
  were genotyped by RFLP pattern. It was observed that 3 (17.6%) were of genotype 
  1 and 14 (82.4%) of genotype 2. Of these, 4 isolates belonged to the 2a subtype 
  and 10 to the 2b subtype (Figure). 
  
DISCUSSION 
Epidemiological investigations demonstrated 
  that GBV-C/HGV RNA prevalence among blood donors ranges from 0.5-4% in the USA, 
  Europe and Japan (Orito et al. 1996, Gutierrez et al. 1997, Nübling et 
  al. 1997, Blair et al. 1998, Mercier et al. 1999, Sauleda et al. 1999) to 10-18.9% 
  in some African countries (Casteling et al. 1998, El-Zayadi et al. 1999, Sathar 
  et al. 1999). In South America, it has also been reported at a varying range 
  from 5.5% in Argentina (Oubiña et al. 1999) to 14.6% in Bolivia (Konomi 
  et al. 1999). In Brazil, rates of 9% and 10% were detected in blood donors in 
  São Paulo and Rio de Janeiro (Southeastern region), respectively (Bassit 
  et al. 1997, Lampe et al. 1998a). In addition, 5.2% and 6.5% of donors with 
  normal and elevated ALT levels were GBV-C/HGV RNA-positive (Pinho et al. 1999). 
  A prevalence of 8.6% was found in Fortaleza (Northeastern region) (Goubau et 
  al. 1999). Thus, the prevalence of 7.1% found in blood donors in Goiânia 
  could be placed in an intermediate position. 
The highest prevalence of GBV-C/HGV 
  RNA was seen in the group from 29 to 39 years (13.5%). A similar finding of 
  age-specific prevalence has been reported by Konomi et al. (1999), with a peak 
  at an age range from 20 to 39 years in healthy Bolivian individuals. In addition, 
  among 170 blood donors in Rio de Janeiro, the seropreva-lence of antibody against 
  GBV-C/HGV envelope E2 protein increased with age, from 5.6% (group with ages 
  between 18 and 24 years) to 35.3% (donors from 43 to 60 years) (Lampe et al. 
  1998b). These data may suggest a role for sexual transmission of GBV-C/HGV. 
  
In the present study, prevalence 
  rates of 5% and 0.8% were found for hepatitis B and C, respectively. Of the 
  17 GBV-C/HGV RNA-positive blood donors, two were positive for anti-HBc, but 
  negative for HBsAg, and none of them was coinfected by HCV. In addition, no 
  association was found between GBV-C/HGV RNA status and serum ALT levels. These 
  data indicate that this virus has been independently widespread in healthy individuals 
  in Central Brazil. 
We observed the characteristics of 
  the GBV-C/HGV RNA-positive donors. Ten individuals had exposure to one or more 
  factors associated with parenteral (30%), sexual (18%), both (6%) and intrafamiliar 
  (6%) transmission. However, it is interesting to note that 40% of the infected 
  donors did not mention any identifiable source of infection, but they earned 
  less than US$ 200 per month and had a low level of education. Thus, low socioeconomic 
  status and poor hygienic conditions occurring in developing countries may contribute 
  to GBV-C/HGV dissemination (Konomi et al. 1999). 
To analyze the genetic diversity 
  of GBV-C/HGV isolates among blood donors in Central Brazil, all GBV-C/HGV RNA-positive 
  samples were genotyped by RFLP. Three samples (17.6%) belonged to genotype 1 
  and the remaining 14 (82.4%) to genotype 2. These data demonstrate the simultaneous 
  circulation of both genotypes, already reported to be predominant in West Africa 
  (genotype 1) and USA/Europe (genotype 2) (Tucker & Smuts 2000). Recently, 
  the same genotypes were detected in 35 serum samples in a Brazilian rural population 
  (Northeastern region); more precisely, 82.9% and 17.1% were characterized as 
  genotypes 2 and 1, respectively (Gallian et al. 1998). Also, Lampe et al. (1998b) 
  showed that 31 isolates from individuals living in Rio de Janeiro (Southeastern 
  region) belonged to three clusters, 2 of which were classified as genotypes 
  1 and 2. The presence of both genotypes in Brazil is likely to reflect the European 
  and African origin of the population. In the present study, genetic diversity 
  of genotype 2 revealed that 4 donors were infected with subtype 2a and 10 with 
  subtype 2b. In Argentina, genotype 2 was also predominant among blood donors, 
  and subtypes 2a and 2b were equally detected (Oubiña et al. 1999). Genotype 
  3 was not observed in Brazilian isolates in spite of immigration from Asian 
  countries, but it was found in other populations of South America, such as native 
  Indians from Colombia (Tanaka et al. 1998) and in Bolivians (Konomi et al. 1999). 
  
In conclusion, our data point out 
  an intermediate endemicity of GBV-C/HGV infection in Central Brazil, and that 
  the parenteral route was the presumed means of virus transmission for only one-third 
  of the infected blood donors. This investigation also demonstrates the simultaneous 
  circulation of genotypes 1 and 2, with a high prevalence of subtype 2b of GBV-C/HGV 
  in the study population. 
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