Hepatitis E is a viral hepatitis (liver inflammation) caused by infection with a virus called hepatitis E virus (HEV). HEV is a positive-sense single-stranded RNA icosahedral virus with a 7.5 kb genome. HEV has a fecal-oral transmission route. Infection with this virus was first documented in 1955 during an outbreak in New Delhi, India.[1]
Molecular biology
Although it was originally classified in the Caliciviridae family, the virus has since been classified into the genus Hepevirus, but was not assigned to a viral family. The virus itself is a small non-enveloped particle.
The genome is approximately 7200 bases in length, is a polyadenylated single-strand RNA molecule that contains three discontinuous and partially overlapping open reading frames (ORFs) along with 5' and 3' cis-acting elements, which have important roles in HEV replication and transcription. ORF1 encode a methyltransferase, protease, helicase and replicase; ORF2 encode the capsid protein and ORF3 encodes a protein of undefined function.
There are currently (2009) approximately 1,600 sequences of HEV that are already available of both human and animal isolates.
Although there is one serotype of this virus, four distinct genotypes have been reported. Genotypes 1 and 2 are restricted to humans and often associated with large outbreaks and epidemics in developing countries with poor sanitation conditions. Genotypes 3 and 4 infect humans, pigs and other animal species and have been responsible for sporadic cases of hepatitis E in both developing and industrialized countries.
An avian virus has been described that is associated with Hepatitis-Splenomegaly syndrome in chickens. This virus is genetically and antigenically related to mammalian HEV and probably represents a new genus in the family.
Replicative virus has been found in the small intestine, lymph nodes, colon as well as the liver of experimentally infected pigs. An in vitro culture system is not yet available. Despite this difficulty a number of vaccine candidates are under investigation.
In a major breakthrough, a three-dimensional, atomic-resolution structure of the hepatitis E capsid protein assembled into a virus-like particle was elucidated by a team of researchers lead by Professor Yizhi Jane Tao at Rice University in Houston, Texas.[2]
Epidemiology
The incidence of hepatitis E is highest in adults between the ages of 15 and 40. Though children often contract this infection as well, they less frequently become symptomatic. Mortality rates are generally low, for Hepatitis E is a “self-limiting” disease, in that it usually goes away by itself and the patient recovers. However, during the duration of the infection (usually several weeks), the disease severely impairs a person’s ability to work, care for family members, and obtain food. Hepatitis E occasionally develops into an acute severe liver disease, and is fatal in about 2% of all cases. Clinically, it is comparable to hepatitis A, but in pregnant women the disease is more often severe and is associated with a clinical syndrome called fulminant hepatic failure. Pregnant women, especially those in the third trimester, suffer an elevated mortality rate from the disease of around 20%.
Patterns
Hepatitis E is prevalent in most developing countries, and common in any country with a hot climate. It is widespread in Southeast Asia, northern and central Africa, India, and Central America. It is spread mainly through fecal contamination of water supplies or food; person-to-person transmission is uncommon. Outbreaks of epidemic Hepatitis E most commonly occur after heavy rainfalls and monsoons because of their disruption of water supplies. Major outbreaks have occurred in New Delhi, India (30,000 cases in 1955-1956), Burma (20,000 cases in 1976-1977), Kashmir, India (52,000 cases in 1978), Kanpur, India (79,000 cases in 1991), and China (100,000 cases between 1986 and 1988).
Animals as a reservoir
Domestic animals have been reported as a reservoir for the hepatitis E virus, with some surveys showing infection rates exceeding 95% among domestic pigs.[3] Transmission after consumption of wild boar meat and uncooked deer meat has been reported as well.[4] The rate of transmission to humans by this route and the public health importance of this are however still unclear.[5]
A number of other small mammals have been identified as potential reservoirs: the Lesser Bandicoot Rat (Bandicota bengalensis), the Black Rat (Rattus rattus brunneusculus) and the Asian House Shrew (Suncus murinus).[6]
Recent outbreaks
In 2004, there were two major outbreaks, both of them in sub-Saharan Africa. There was an outbreak in Chad in which, as of September 27 there were 1,442 reported cases and 46 deaths. In Sudan, which has been troubled with conflict recently (see, Darfur conflict), they are also suffering from a severe Hepatitis E epidemic. As of September 28, there were 6,861 cases and 87 deaths, mainly in the West Darfur Region. UNICEF, Doctors Without Borders, the Red Cross, and other international health organizations are currently working to increase the availability of soap, dig new wells, and chlorinate water supplies and reserves. However, the existing resources are still not enough, and more personnel and funds are severely needed in the region to assure the health and welfare of the people. Increasingly, hepatitis E is being seen in developed nations with reports of cases in the UK, US and Japan. The disease is thought to be a zoonosis in that animals are thought to be the source. Both deer and pigs have been implicated.
Prevention
Improving sanitation is the most important measure, which consists of proper treatment and disposal of human waste, higher standards for public water supplies, improved personal hygiene procedures and sanitary food preparation. Thus, prevention strategies of this disease are similar to those of many others that plague developing nations, and they require large-scale international financing of water supply and water treatment projects. A vaccine based on recombinant viral proteins has been developed and recently tested in a high-risk population (military personnel of a developing country).[7] The vaccine appeared to be effective and safe, but further studies are needed to assess the long-term protection and the cost-effectiveness of hepatitis E vaccination.
Additional hepatits E viruses
A new virus designated rat Hepatitis E virus has been isolated.[8]
References
- ^ Gupta DN, Smetana HF (1957). "The histopathology of viral hepatitis as seen in the Delhi epidemic (1955-56)". Indian J. Med. Res. 45 (Suppl.): 101–13. PMID 13438544.
- ^ http://www.rice.edu/nationalmedia/news2009-07-21-HEV.shtml
- ^ Satou K, Nishiura H (2007). "Transmission dynamics of hepatitis E among swine: potential impact upon human infection". BMC Vet. Res. 3: 9. doi:10.1186/1746-6148-3-9. PMID 17493260. http://www.biomedcentral.com/1746-6148/3/9.
- ^ Li TC, Chijiwa K, Sera N, et al. (2005). "Hepatitis E virus transmission from wild boar meat". Emerging Infect. Dis. 11 (12): 1958–60. PMID 16485490. http://www.cdc.gov/ncidod/EID/vol11no12/05-1041.htm.
- ^ Kuniholm MH & Nelson KE (2008). "Of organ meats and Hepatitis E virus: One part of a larger puzzle Is solved". J Infect Dis 198 (12): 1727–1728. doi:10.1086/593212.
- ^ RatBehavior.org
- ^ Shrestha MP, Scott RM, Joshi DM, et al. (2007). "Safety and efficacy of a recombinant hepatitis E vaccine". N. Engl. J. Med. 356 (9): 895–903. doi:10.1056/NEJMoa061847. PMID 17329696.
- ^ Johne R, Plenge-Bönig A, Hess M, Ulrich RG, Reetz J, Schielke A.(2009) Detection of a novel hepatitis E-like virus in faeces of wild rats using a nested broad-spectrum RT-PCR. J. Gen Virol.
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