PERSPECTIVE Running Like Vater — The Omnipresence of Hepaths E GLOBAL HEALTH Running Like Water — The Omnipresence of Hepatitis E ‘Suzanne U. Emerson, Ph.D., and Robert H. Purcell, M.D. Hepatitis E virus (HEV), originally identified as the culprit in massive waterbome epidemics of acute hepatitis in Asia, is now commanding attention in. regions of Sudan and Iraq. And once again, con- taminated water is implicated. Between May and August of 2004, almost 4000 suspected cases of hepatitis E were reported by health clinics in the Greater Darfur region of Sudan, where civil con- flict has forced the intemal displacement of ap- proximately 15 percent ofthe population. Sudanese refugees who fled to camps in neighboring Chad have fared no better, and more than 1000 suspect- edcases of hepatitis E were identified between june and September. In Img, where conflict also rages, probable cases of hepatitis E were identified in Sadr City in March and, more recently, in Mahmudiya, about 25 miles south of Baghdad. Although the ‘number of reported cases in Iraqisin the hundreds rather than the thousands, the lower nurabers could. well reflect underreporting and the lack ofa rou tine diagnostic test for hepatitis E. The crowded, unsanitary conditions faced by the Sudanese refu- gees and the inadequate sewage treatment and er- ratiewater supplies in ag have permitted the virus tothive. Itisnot sumprising that hepatitis Bis now erupt- ing in Sudan and Iraq. The conditions are conda- to viral dissemination, and outbreaks of her- is E have occurred previously in Africa (see map). ‘More than 2000 cases occurred in 1985 and 1985 in Bthiopian refugee camps in Somalia and Sudan. Hepatitis E also causes sporadic hepatitis and is. the second most common cause ofstch disease in North Affica andthe Middle Bast. Thereis no treat- ment for hepatitis &, and there is not yet a vaccine to prevent it, although a recombinant vaccine has just undergone clinical trials in Nepal. Diagnosis cannot be made on the basis of clinical presenta- tion but, rather, requires laboratory amplification of vial genomes found in serum and feces during the acute phase of the disease or detection of spe- cific antibodies during the convalescent phase. D- agnostic serologic tests are available in some parts, ofthe worldbutarenotlicensed in many counties, including the United States. Fortunately, HEV isnot commonly transmitted from person to person, 50 improving sanitation and boiling or chemically pu- riffing the water can substantially reduce the bur- den of disease. ‘The vim that causes hepatitis E was identified only recently (sce diagram). The first evidence that HEV existed was obtained in 1980 through a pro- cess of exclusion. Once specific tests had been de- ‘eloped for hepatitis A virus HAV), the otherenter- sencty ute 25128 ww.ngyucone “eetwasna, 2004 2367 a |PERSPECTIVE Hepatitis virus aa (eonenloped icosahedral) ae ANA Or oeele Model ofa Hepatic £ Vis Pate. ‘Theheoaits Eviushas rot been studied at high resolu tion this medel is based on current inowledge about re ‘combinant panicles. Adapted fom Ying et al ‘cally transmitted hepatitis virus, it became clear that mzjor waterborne epidemics of hepatitis in In- dia were eaused not by HAV but, rather, by a previ- ously unrecognized agent. We now know that the hepatitis caused by these two viruses is clinically indistinguishable and that many outbreaks origi- nally atributed to HAY, including somes far back asthe Crusades, were most likely due to HEY. Patients with hepatitis Ecan present with signs and symptoms common to all viral hepatitis: jaun- dice, anorexia, hepatomegaly, abdominal pain, nau- ses, vomiting, and fever. The incubation period ranges from three to eight weeks, and jaundice can persist for several weeks. Although hepatitis Enev- ex progresses toa chronic condition and fll ecov- ey is usual in most groups, mortality rates oF 0.5 to 4 percent in the general population and, for ua- known reasons, up to 20 peeent among pregnant women have been reported. Much about the epidemiology of hepatitis Eis unknows, Ouebresks are most common in tropical and subtopical regions and are rare in temperate climates. Contamineted water supplies have been 4 feequent source of epidemics and reflect the fact that HEY, like HAV, is excreted in the feces and can survive in sewage. Intuitively, one would expect these two hepatitis viruses to have similar epide- miology, but thisisnoc thecase. n India, as in many other developing countries where both vicuses are endemic, infection with HAV, as measured by anti- body seroprevalence, isalmost universally acquired by ive years of age, when most infections are in- apparent, whereas HEV most commonly infects young adults. Surprisingly, antibodies to HEV are ‘ound in only 30040 percent of adults. Incontrast, Running Like Water — The Omnipresence of HepattisE in Egypt, where similar environmental conditions that are conducive to fecal-oral transmission ex ist, the prevalence of antibodies to HEY already exceeds 60 percent by 10 years oFage. Why thept tem ofantibody acquisition should be so differeat inthese two countries remains unexplained —and isas puzalingas he question of why the age-strat- fied seroprevalence of ant-HAV antibodies in India | is so dissimilar to that of ant-HEV antibodies. Although exceedingly rare, locally acquired hey atitis E has now been found in many industrial ized countries, including the United States, Japan, and countries of the European Union. However, the prevalence of antibodies to HEV is much higher than expected in these countries (as high as 20per- cent among blood donors in some regions of the United States), given the ratty of the disease, Also, many species of animals, from rodents to monkeys, have similar antibodies. A vius closely related to human HEV bas been isolated from swine in many developing and industrialized countries, including the United States. Therefore, the specter of hepi- tits E as.a zoonotic disease that ean be acquired from animalshas arisen. Indeed, recent clusters oF cases of hepatitis Ein Japan have been traced to the ingestion of undercooked deer meat and pig liver. icremains to be determined how commonly and by what other mechanism the virus may be transmit. ted from animals to humans, butin view ofthe large umber of species potentially involved, itis anarez that requires exploration. HEV is pethaps best described as an opporti- nistic pathogen. Both the virus and the disease ap- pear tobe virtually everywhere, butthe frequency of disease varies tremendously according to region Strains that cause sporadic cases of hepatitis E in many developing countries have the potential to «cause explosive epidemics when the infrastructure breaks down, asithas in Sadan and iraq, One might surmise that the strains that are already present inindustialized countries have the same potential; iis simply our good fortune that they have so far been held in check by better sanitation. Ors Emeson snd Purcell ae ited i coimventersona patent or hepatitis vacive ewred bythe US. rovertment From the Molecular Hepat Scion (U6) and the Hepat Vines Secton (LHP], Laboratory of Ifectovs Direser, Ne Sonal intitute f Alergy and infctows Oiscesea, National nt tutes ofeath, Batheada, Md. 1 Xing L. Kato K, LT, ea. Recombinart hepatitis cps protein sleaseerebles into a dual corain T=! patie present Ingnaive vu eitoner.Vrlony199:2653545.