less likely to respond to treatment when infected with genotypes 1 or 4. the substantial proportion of this lack of response to treatment is proposed to be caused by a single-nucleotide polymorphism (snp) on chromosome 19 of the human genome that is predictive of treatment success. hcv genotypes 1 and 4 have been distributed endemically in overlapping areas of west and central africa, infecting for centuries human populations carrying the genetic polymorphism in question. this has prompted scientists to suggest that the protracted persistence of hcv genotypes 1 and 4 in people of african origin is an evolutionary adaptation of hcv over many centuries to these populations’ immunogenetic responses. infection with one genotype does not confer immunity against others, and concurrent infection with two strains is possible. in most of these cases, one of the strains outcompetes the other in a short time. this finding may be useful in treatment, in replacing strains non-responsive to medication with others easier to treat. recombination when two viruses infect the same cell, genetic recombination may occur. although infrequent, hcv recombination has been observed between different genotypes, between subtypes of the same genotype and even between strains of the same subtype. epidemiology further information: hepatitis c § epidemiology hepatitis c virus is predominantly a blood-borne virus, with very low risk of sexual or vertical transmission. because of this mode of spread the key groups at risk are intravenous drug users (idus), recipients of blood products and sometimes patients on haemodialysis. common setting for transmission of hcv is also intra-hospital (nosocomial) transmission, when practices of hygiene and sterilization are not correctly followed in the clinic. a number of cultural or ritual practices have been proposed as a potential historical mode of spread for hcv, including circumcision, genital mutilation, ritual scarification, traditional tattooing and acupuncture. it has also been argued that given the extremely prolonged periods of persistence of hcv in humans, even very low and undetectable rates of mechanical transmission via biting insects may be sufficient to maintain endemic infection in the tropics, where people receive large number of insect bites. evolution identification of the origin of this virus has been difficult but genotypes 1 and 4 appear to share a common origin. a bayesian analysis suggests that the major genotypes diverged about 300–400 years ago from the common ancestor virus. the minor genotypes diverged about 200 years ago from their major genotypes. all of the extant genotypes appear to have evolved from genotype 1 subtype 1b. a study of genotype 6 strains suggests an earlier date of evolution: approximately 1,100 to 1,350 years before present. the estimated rate of mutation was 1.8 × 10−4. an experimental study estimated the mutation rate at 2.5–2.9 × 10−3 base substitutions per site per year. this genotype may be the ancestor of the other genotypes. a study of european, us and japanese isolates suggested that the date of origin of genotype 1b was approximately in the year 1925. the estimated dates of origin of types 2a and 3a were 1917 and 1943 respectively. the time of divergence of types 1a and 1b was estimated to be 200–300 years. a study of genotype 1a and 1b estimated the dates of origin to be 1914–1930 for type 1a and 1911–1944 for type 1b. both types 1a and 1b underwent massive expansions in their effective population size between 1940 and 1960. the expansion of hcv subtype 1b preceded that of subtype 1a by at least 16 years. both types appear to have spread from the developed world to the developing world. the genotype 2 strains from africa can be divided into four clades that correlate with their country of origin: (1) cameroon and central african republic (2) benin, ghana and burkina faso (3) gambia, guinea, guinea-bissau and senegal (4) madagascar. there is also strong evidence for the dissemination of hcv genotype 2 from west africa to the caribbean by the trans-atlantic slave trade. genotype 3 is thought to have its origin in south east asia. these dates from these various countries suggests that this virus may have evolved in south east asia and was spread to west africa by traders from western europe. it was later introduced into japan once that country's self-imposed isolation was lifted. once introduced to a country its spread has been influenced by many local factors including blood transfusions, vaccination programmes, intravenous drug use and treatment regimes. given the reduction in the rate of spread once screening for hcv in blood products was implemented in the 1990s, it would seem that previously blood transfusion was an important method of spread. additional work is required to determine the dates of evolution of the various genotypes and the timing of their spread across the globe. vaccination main article: hepatitis c vaccine unlike hepatitis a and b, there is currently no vaccine to prevent hepatitis c infection. current research the study of hcv has been hampered by the narrow host range of hcv. the use of replicons has been successful but these have only been recently discovered. hcv, as with most rna viruses, exists as a viral quasispecies, making it very difficult to isolate a single strain or receptor type for study. current research is focused on small-molecule inhibitors of the viral protease, rna polymerase and other nonstructural genes. two agents—boceprevir by merck and telaprevir by vertex pharmaceuticals—both inhibitors of ns3 protease were approved for use on may 13, 2011 and may 23, 2011 respectively. a possible association between low vitamin d levels and a poor response to treatment has been reported. in vitro work has shown that vitamin d may be able to reduce viral replication. while this work looks promising the results of clinical trials are pending. however, it has been proposed that vitamin d supplementation is important in addition to standard treatment, in order to enhance treatment response. naringenin, a flavonoid found in grapefruit and other fruits and herbs, has been shown to block the assembly of intracellular infectious viral particles without affecting intracellular levels of the viral rna or protein. other agents that are under investigation include nucleoside and nucleotide analogue inhibitors and non-nucleoside inhibitors of the rna-dependent rna polymerase, inhibitors of nsp5a, and host-targeted compounds such as cyclophilin inhibitors and silibinin. sofosbuvir for use against chronic hepatitis c infection was approved by the fda on december 6, 2013. it has been reported to be the first drug that has demonstrated safety and efficacy to treat certain types of hcv infection without the need for co-administration of interferon. on november 22, the fda approved simeprevir for use in combination with peginterferon-alfa and ribavirin. simeprevir has been approved in japan for the treatment of chronic hepatitis c infection, genotype 1. there is also current experimental research on non drug related therapies. oxymatrine, for example, is a root extract found in the continent of asia that has been reported to have antiviral activity against hcv in cell cultures and animal studies. small and promising human trials have shown beneficial results and no serious side effects, but they were too small to generalize conclusions. on october 5th, 2020, it was announced that harvey j. alter, michael houghton, and charles m. rice had been awarded the 2020 nobel prize in physiology or medicine for the discovery of hcv.