countries. no hepatitis e vaccine is licensed for use in the united states. the exception is china; after more than a year of scrutiny and inspection by china's state food and drug administration (sfda), a hepatitis e vaccine developed by chinese scientists was available at the end of 2012. the vaccine—called hev 239 by its developer xiamen innovax biotech—was approved for prevention of hepatitis e in 2012 by the chinese ministry of science and technology, following a controlled trial on 100,000+ people from jiangsu province where none of those vaccinated became infected during a 12-month period, compared to 15 in the group given placebo. the first vaccine batches came out of innovax's factory in late october 2012, to be sold to chinese distributors. due to lack of evidence, the world health organization has not made a recommendation regarding routine use of the hev 239 vaccine as of 2015. its 2015 position was that national authorities may decide to use the vaccine based on their local epidemiology. treatment there is no drug that has established safety and effectiveness for hepatitis e, and there have been no large randomized clinical trials of antiviral drugs. reviews of existing small studies suggest that ribavirin can be considered effective in immunocompromised people who have developed chronic infection. chronic hev infection is associated with immunosuppressive therapies, and when that happens in individuals with solid-organ transplantation, reducing immunosuppressive medications can result in clearance of hev in one third of patients. epidemiology the hepatitis e virus causes around 20 million infections a year. these result in around three million acute illnesses and resulted in 44,000 deaths during 2015. pregnant women are particularly at risk of complications due to hev infection, who can develop an acute form of the disease that is fatal in 30% of cases or more. hev is a major cause of illness and of death in the developing world and disproportionate cause of deaths among pregnant women. hepatitis e is endemic in central asia, while central america and the middle east have reported outbreaks. increasingly, hepatitis e is being seen in developed nations, with reports in 2015 of 848 cases of hepatitis e virus infection in england and wales. recent outbreaks in october 2007, an epidemic of hepatitis e occurred in kitgum district of northern uganda. this outbreak progressed to become one of the largest known hepatitis e outbreaks in the world. by june 2009, it had resulted in illness in 10,196 persons and 160 deaths. the aforementioned outbreak occurred despite no previous epidemics having been documented in the country, women were the most affected by hev. namibia, africa in july 2012, an outbreak was reported in south sudanese refugee camps in maban county near the sudan border. south sudan's ministry of health reported over 400 cases and 16 fatalities as of 13 september 2012. progressing further, as of 2 february 2013, 88 died due to the outbreak. the medical charity medecins sans frontieres said it treated almost 4000 people. in april 2014, an outbreak in the biratnagar municipality of nepal resulted in infection of over 6000 locals and at least 9 dead. during an outbreak in namibia, the number of affected people rose from 490 in january 2018, to 5014 (with 42 deaths) by april 2019, to 6151 cases (with 56 deaths) by august 2019; the who estimated that the case fatality rate was 0.9%. in hong kong in may 2020, there were at least 10 cases of hepatitis e that were transmitted by rats, and possibly hundreds of cases that had a transmission mechanism that is not fully understood. evolution the strains of hev that exist today may have arisen from a shared ancestor virus 536 to 1344 years ago. another analysis has dated the origin of hepatitis e to ~6000 years ago, with a suggestion that this was associated with domestication of pigs. at some point, two clades may have diverged — an anthropotropic form and an enzootic form — which subsequently evolved into genotypes 1 and 2 and genotypes 3 and 4, respectively. whereas genotype 2 remains less commonly detected than other genotypes, genetic evolutionary analyses suggest that genotypes 1, 3, and 4 have spread substantially during the past 100 years.