Lorena Jemeršić, Jelena Prpić, Ivana Lojkić, Dragan Brnić
Virološki odjel, Hrvatski veterinarski institut
Sažetak
Hepatitis E (HE) je virusna zarazna bolest ljudi uzrokovana RNK virusom iz porodice Hepeviridae, potporodice Orthohepevirinae, roda Paslahepevirus. Tijek i ishod infekcije značajno variraju ovisno o imunosnom statusu čovjeka, ali i genotipu virusa. Dok su neki genotipovi iznimno virulentni i specifični samo za ljude (npr. 1 i 2), neki dovode do blažih upalnih procesa u jetri, pojave kroniciteta, izvanhepatičkih upalnih procesa, a zoonotskog su karaktera (3, 4, i 8). Njima su prirodni rezervoari domaće i divlje životinje, a protutijela za virus HE su nađena u nizu različitih vrsta toplokrvnih i hladnokrvnih životinja. Međutim, do danas se jedinim pravim rezervoarima virusa HE smatraju domaća i divlja svinja. U Hrvatskoj istraživanja prevalencije HE u životinja počinju 2009. godine kada se dokazuje 15 % inficiranih domaćih svinja i 11 % divljih, a protutijela su dokazana u obje vrste u oko 30 % pretraženih svinja, dok je RNK virusa 2019. godine dokazana u Hrvatskoj jedino još u žutogrlog miša. Prvi autohtoni slučaj u čovjeka dokazan je 2012. godine. Prevalencija u zdravih ljudi prema podacima Hrvatskog zavoda za transfuzijsku medicinu iznosi oko 20,2 %, (HEV IgG) i 4,4 % (IgM), međutim broj klinički pozitivnih slučajeva ostaje nizak, tj. iznosi svega 11% od svih akutnih hepatitisa u Hrvatskoj koji nisu dijagnosticirani kao hepatitis A, B ili C. Filogenetska analiza izolata izdvojenih iz domaće svinje, divlje svinje, miša i čovjeka, potvrđuje međuvrsni prijenos uzročnika, odnosno isti izvor infekcije. HE ne dovodi do znakova bolesti u životinja te predstavlja tihu infekciju do pojave u čovjeka.
Prema ocjeni Svjetske zdravstvene organizacije, jedna od emergentnih infekcija koja predstavlja ozbiljnu ugrozu za Hrvatsku, ali i cjelovitu Europu je krimsko-kongoanska hemoragijska groznica (CCHF). CCHF je virusna bolest koja se prenosi na čovjeka prvenstveno ugrizom zaraženog krpelja iz porodice Ixodidae, roda Hyalloma, ali prijenosnici mogu biti i krpelji iz rodova Rhipicephalus, Boophilus, Dermacentor i Ixodes. Uzročnik je infekcije RNK virus iz porodice Bunyaviridae, roda Nairovirus.
CCHF je jedna od najsmrtonosnijih hemoragijskih infekcija ljudi, gdje je očekivani mortalitet 10-80%, a najčešće iznosi 30%. Bolest se javlja naglo pojavom groznice, snažnih glavobolja, drhtavice, mijalgije te probavnih smetnji, a često je praćena i krvarenjima po koži i sluznicama. Smrt nastupa zbog sustavnog zatajivanja vitalnih organa (bubrega, jetre ili pluća). Čovjek može oboljeti i pijući kontaminirano mlijeko životinja (govedo, ovca i koza), ali i izravnim dodirom s ekskretima i sekretima inficiranih životinja zbog čega su veterinari i osobe koje dolaze u dodir s krvlju i organima životinja (lovci) od većeg rizika za infekciju. Posljednjih godina zabilježen je porast broja oboljelog medicinskog osoblja koji su bili u dodiru sa zaraženim pacijentima. CCHF je endemična infekcija u 52 države Svijeta. Na području Europe CCHF je endemska u državama bivšeg SSSR-a, Albaniji, Bugarskoj i Kosovu, a prijavljena je infekcija ljudi u Grčkoj i Turskoj (2002.). CCHF je dokazana i u Španjolskoj (2013.). Izravni i neizravni dokaz CCHF je potvrđen u konja, goveda, ovce, koze i psa, a od divljih životinja najznačajniji su rezervoari zec i šumski jež. Premda životinje u pravilu ne pokazuju znakove infekcije, važna su karika u lancu prijenosa infekcije bilo putem prijenosa virusa ugrizom krpelja, izravnim dodirom ili konzumacijom zaraženog mlijeka. Do danas, CCHF nije dokazana u Hrvatskoj.
Za sada ne postoje učinkovita cjepiva protiv CCHF i HE, niti u većine država svijeta postoje službeni programi dijagnostike infekcija u domaćih i divljih životinja usprkos težini kliničke slike bolesti i mogućeg letalnog ishoda. Ministarstvo poljoprivrede je podržalo istraživanje HE u domaćih i divljih svinja 2016. godine što je značajno pomoglo razumijevanju epidemiologije pojave bolesti i dovelo do saznanja da je HE, kao i u većini država Europe poprimio endemske značajke.
Premda vrlo različite, obje bolesti nemaju specifičnu terapiju. Antivirusni lijekovi (pegilirani interferon i/ili ribavirin) djeluju npr. na smanjivanje titra virusa HE nakon primjene, ali dok se ne uspostave mjere zaštite životinja od infekcije, i to CCHF prvenstveno nadzorom vektora, odnosno u slučaju HE onemogućavanjem ulaska virusa u uzgoj svinja, obje bolesti mogu uzrokovati značajne javnozdravstvene probleme, jedna tek u dolasku, dok je druga već endemska.
Ključne riječi: zoonoze, hepatitis E, krimsko-kongoanska hemoragična groznica, javno zdravstvo, životinje.
AN EXAMPLE OF AN ENDEMIC AND POSSIBLE EMERGENT VIRAL ZOONOSIS IN CROATIA – HEPATITIS E AND CRIMEAN-CONGO HEMORRHAGIC FEVER
Lorena Jemeršić, Jelena Prpić, Ivana Lojkić, Dragan Brnić
Abstract
Z oonoses, especially of viral origin are becoming one of the most important public health concerns, globally. Climate change, land reclamation, the presence of appropriate vectors, animal and human migration, and hunting contribute significantly to their appearance and spread in countries where they were not present until recently.Hepatitis E (HE) is a viral infectious disease of humans caused by an RNA virus from the family Hepeviridae, subfamily Orthohepevirinae, genus Paslahepevirus. The course and outcome of the infection vary significantly depending on the im- mune status of the person, as well as the genotype of the virus. While some genotypes are extremely virulent and specific only to humans such as genotype 1 and 2, some lead to milder inflammatory processes in the liver, the appearance of chronicity, extrahepatic inflammatory processes, and show a zoonotic potential (3, 4, and 8). Their natural reservoirs are domestic and wild animals, and antibodies to the HE virus have been found in a number of different species of warm- and cold-blooded animals. However, to date, domestic and wild pigs are considered the only real reservoirs of HE virus.
In Croatia, research on the prevalence of HE in animals began in 2009, when 15% of infected domestic pigs and 11% of wild pigs were found to be actively infected, while antibodies were found in both species in about 30% of tested animals. In 2019, the RNA of the virus was found in Croatia in the yellow-throated mouse as the only other animal species that was found positive for viral RNA in Croatia. The first autochthonous case in humans was proven in 2012. According to the data of the Croatian Institute for Transfusion Medicine, the prevalence in healthy people is about 20.2% (HEV IgG) and 4.4% (IgM), respectively, however, the number of clinically positive cases remains low, i.e. it represents 11% of all acute viral hepatitis cases in Croatia that have not been diagnosed as hepatitis A, B or C. Phylogenetic analysis of isolates derived from domestic pigs, wild boars, mouse and humans confirms the interspecies transmission of the causative agent, i.e. the same source of infection. HE does not cause signs of disease in animals and represents a silent infection until it appears in humans.
According to the assessment of the World Health Organization, one of the emerging infections that represents a serious threat to Croatia, but also to the whole of Europe, is the Crimean-Congo hemorrhagic fever (CCHF). CCHF is a viral disease that is transmitted to humans primarily by the bite of an infected tick from the family Ixodidae, genus Hyalloma, but ticks from the genera Rhipicephalus, Boophilus, Dermacentor and Ixodes can also be carriers. The causative agent of the infection is an RNA virus from the family Bunyaviridae, genus Nairovirus.
CCHF is one of the deadliest human hemorrhagic infections, where the expected mortality is 10-80%, with an average of 30%. The disease appears suddenly with the onset of fever, severe headaches, shivering, myalgia and indigestion, and is often accompanied by bleeding on the skin and mucous membranes. Death occurs due to systemic failure of vital organs (kidneys, liver or lungs). Humans can also get infected by drinking fresh contaminated milk (from cattle, sheep and goats), but also by direct contact with the excreta and secretions of infected animals, which is why veterinarians and people who come into contact with the blood and organs of animals (hunters) are at a higher risk of infection. In recent years, there has been an increase in the number of CCHF virus transmission to medical personnel who were in contact with infected patients. CCHF is endemic in 52 countries of the world. In Europe, CCHF is endemic in the countries of the former USSR, Albania, Bulgaria and Kosovo, and human infection has been reported in Greece and Turkey (2002). CCHF was also proven in Spain (2013).
Direct and indirect evidence of CCHF infection has been confirmed in horses, cattle, sheep, goats and dogs, while among wild animals the most important reservoirs are rabbits and hedgehogs.
Although animals usually do not show signs of infection, they are an important link in the chain of transmission of infection either through the transmission of the virus through a tick bite, direct contact or consumption of infected milk. To date, CCHF has not been proven in Croatia.Currently, there are no effective vaccines against CCHF and HE, nor in most countries of the world official surveillance programs for detecting the causative agents in domestic and wild animals, exist, despite the severity of the clinical picture of the disease and the possible fatal outcome. However, the input of The Ministry of Agriculture that supported research on HE in domestic and wild pigs in 2016, significantly contributed in understanding the epidemiology of the disease and led to the knowledge that HE, as in most European countries, has acquired endemic features in Croatia.
Although very different, both diseases have no specific treatment. Antiviral drugs (pegylated interferon and/or ribavirin) may be efficient in to reducing the titer of HE virus after administration, but until measures are established to protect animals from infection, namely CCHF primarily by vector control, or in the case of HE by preventing the virus from entering pig farming systems, both diseases can cause significant public health problems, while one is just emerging, the other is already endemic.
Key words: zoonoses, hepatitis E, Crimean Congo heorrhagic fever, public health, animals.
Vezano (hepatitis E, krimsko-kongoanska hemoragična groznica):
- Radi suzbijanja hepatitisa E svinjetinu je nužno dobro termički obraditi
- Infekcije virusom hepatitisa E u konja, pasa i mačaka na području Republike Hrvatske
- Seroprevalencija virusa hepatitisa E u krava s ruralnih područja južne Italije
- Novi i zanemareni virusi zoonotske važnosti u Hrvatskoj
- Virusne i vektorski prenosive virusne zoonoze u Srbiji u kontekstu “Jednog zdravlja”