[en] Q fever is a zoonosis caused by Coxiella burnetii, an intracellular bacterium thataffects domestic and wild animals and causes abortion and reproductive problems in ruminants. The main sources of C. burnetii infection are cattle, sheep and goats. The most important route of human Q fever infection is inhalation of contaminated aerosols or dust containing C. burnetii shed by infected animals, mainly at parturition when infected females shed great numbers of bacteria through birth products, vaginal mucus, milk and faeces. As is the case for many other zoonoses, control of Q fever in animals will influence the incidence of this disease in humans, highlighting the importance of the implementation of adequate control options to reduce human infection risk. At the time this work started, sheep were considered to be an important source of Q fever infection in the Basque Country, but there was a lack of information on the status of C. burnetii infection in cattle and goats in the region. Also, little was known about the prevalence of C. burnetii in wildlife in the Basque Country. Regarding control methods, antibiotic treatment with oxitetracycline (OTC) had been used to reduce the number of abortions by C. burnetii in sheep, but its efficacy in decreasing the rate of infection after a C. burnetii outbreak had not been accurately assessed. Similarly, no data were available concerning the efficacy of an inactivated phase I vaccine in highly naturally infected sheep flocks. In this PhD Thesis, a serological study was conducted with the aim of investigating the seroprevalence of C. burnetii in livestock in the Basque Country. Results confirmed that sheep are the main source of infection with a herd seroprevalence of 74%, followed by goats (45%) and cattle (43%); average individual C. burnetii seroprevalence observed was 11.8%, 8.7% and 6.7% in sheep, goats and cattle, respectively. To investigate the role of wildlife, a molecular survey was conducted to estimate the distribution and incidence of C. burnetii infection in wildlife in the Basque Country. C. burnetii DNA was detected in 5.1% of roe deer, 4.3% of wild boar, 9.1% of hares; and, among wild birds, in 11% of vultures and 14% black kites. These species should therefore be considered as potential sources of infection and could also act as sentinel for the presence of infection foci. All the adult ticks analyzed were negative for C. burnetii, suggesting that ticks do not play an important role in the transmission of C. burnetii in this area. Due to the high seroprevalence of C. burnetii found in sheep flocks in the Basque Country, several studies were conducted with the purpose of evaluating the different options available to control Q fever in highly infected sheep flocks. With this purpose, the efficacy of antibiotic treatment with OTC in an infected dairy sheep flock was assessed. Results showed that OTC did neither prevent the shedding of C. burnetii nor limited the duration of bacterial excretion. In addition, OTC did not reduce the bacterial load excretion and no beneficial residual effect in the next lambing season was observed in terms of reducing or eliminating bacterial excretion in previously treated ewes. Nevertheless, a decrease in the number of abortions was observed. In addition, this study showed that the main routes of C. burnetii shedding in sheep were vaginal discharges and faeces, and to a lesser extent, milk. Whereas shedding through milk was sporadic and concentrated during the first month after parturition, vaginal and faecal shedding continued for longer. A further study was designed to assess the efficacy of vaccination in highly naturallyinfected sheep flocks. Animal vaccination was proposed due to the good results reported elsewhere in preventing shedding in non-infected susceptible animals. One year after vaccination of four sheep flocks (including a non-vaccinated control group in each flock) with a phase I vaccine, a reduction was observed in the percentage of abortions, in the number of shedders and in the bacterial mean load. Besides, the seroconversion of non-vaccinated young animals indicated the existence of an active infection, suggesting that the vaccine could have had a possible effect in protecting susceptible animals. A similar reduction was nevertheless also observed in the group of unvaccinated animals, so that the possibility of a natural self-limitation of the infection could not be discarded, as it has been described before. Since vaccination during a single year did not show a significant effect in reducing the number of shedders and the bacterial load excreted, a four-year vaccination scheme was designed and evaluated on a highly naturally infected flock. The high percentage of animal shedders found during the first year of vaccination decreased considerably in the second year and shedding completely disappeared in the last two years of the vaccination programme. However, C. burnetii was still present in the environment after completion of the four-year vaccination programme since air samples collected during the third year and dust samples taken from solid surfaces during the last year tested positive. These results would suggest that at least five years of vaccination are needed to reduce environmental contamination with C. burnetii to minimum levels. In summary, it can be concluded that C. burnetii is involved both in the domestic and the wild cycles in the Basque Country, being sheep one of the most important reservoirs for C. burnetii in this region. It is also noteworthy the role of wild boar, roe deer, hares and carrion wild birds as potential reservoirs of C. burnetii. Finally, this study has provided valuable information on different strategies for Q fever infection control that could be implemented in case of an outbreak of Q fever in a sheep flocks in order to limit economic losses and reduce risk for human infection.

[eu] Q sukarra mundu osoan zehar zabaldurik dagoen zoonosi bat da eta Coxiella burnetii deritzon zelula barneko bakterio batek eragiten du gaixotasuna. Etxeko animaliak zein animalia basatiak infektatzeko gai da, abortu eta ugalketa arazoak eraginez. Gizakiarentzat infekzio iturri nagusia ardi, ahuntz eta behi aziendek osatzen dute, izan ere, hauek infektaturik aurkitzen badira, bakterioa kanporatzen dute erditze produktuekin batera, baginako fluidoekin, esnea zein gorotzen bitartez, aerosolak sortuz eta arnasten duten indibiduo sentiberak infektatuz. Beste hainbat gaixotasun zoonotikorekin gertatzen den moduan, animaliengan egiten den Q sukarra-rekiko kontrolak eragina izango du gaixotasun honek gizakiarengan izan dezakeen agerrerak, beraz garrantzitsua da infekzioarekiko kontrol neurriak ezartzea. Lan hau burutu den arte, ardiaziendek C. burnetii-ren gordailu gisa jokatzen dutela jakina zen Euskal Autonomia Erkidego-an, hala ere, ahuntz eta behi azienden egoera ezezaguna zen. Halaber, animalia basatiengan C. burnetii-ren prebalentziari buruzko ikerketa gutxi ezagutzen ziren. Gainera, Q sukarrak eragindako abortu-agerraldi baten aurrean, oxitetraziklina (OTC) botika bidezko tratamendua eraginkorra ote zen ez zegoen garbi. Era berean, naturalki infektaturiko ardi-aziendarengan, I fase-ko txertoaren eragina ezezaguna zen. Era honetara, lehenik eta behin, Euskal Autonomia Erkidego-an C. burnetii-ren seroprebalentzia jakiteko ikerketa burutu zen, ardi-aziendak Q sukarra-ren transmisio iturri nagusi gisa jokatzen jarraitzen zuela egiaztatuz. Ardiaziendarengan %74-eko seroprebalentzia detektatu zen, eta baxuagoa izan zen ahuntz (%45) eta behi (%43) aziendengan. Seroprebalentzia indibidualak %11,8, %8,7 eta %6,7-koak izan ziren hurrenez hurren. Gainera, C. burnetii-k Euskal Autonomia Erkidego-an ziklo basatiarengan izan zezakeen garrantzia ere aztertu zen eta C. burnetii-ren ADN-a aurkitu zen orkatz (%5,1), basurde (%4,3), erbi (%9,1) eta hegaztia basatien artean, sai arre (%11) eta miru beltzengan (%14). Emaitza hauek aditzera ematen dute espezie hauek Q sukarra-ren agerraldietan gordailu zein zentinela gisa joka dezaketela. Animalia hauengan jasotako akainak PCR bitartez aztertu ondoren emaitza guztiak negatibo izan ziren, beraz ixodidoek Q sukarra transmititzeko orduan paper garrantzitsua jokatzen ez dutela iradoki zen. Euskal Autonomia Erkidego-ko ardi-aziendengan aurkitutako seroprebalentzia altua ikusita, zenbait ikerketa burutu ziren infektatutako ardi-aziendengan Q sukarra-ren agerrera kontrolatzeko aukera ezberdinak aztertuz. Era honetara, OTC botika bidezko tratamendu baten eraginkortasuna frogatu zen infektaturiko ardi-azienda batengan eta zera ikusi zen: tratamenduak ez zuela bakterioaren kanporatze denbora gutxiagotzen, ez zela animaliakanporatzaileen kopurua murrizten, ezta kanporatutako bakaterio karga ere, baina abortu kopurua txikiagoa izan zen. Bestalde, ez zen OTC-aren hondakinik antzeman hurrengo erditzean. Gainera ikerketa honek erakutsi zuen ardi-aziendengan C. burnetiiren kanporaketa fluido baginal eta gorotzen bitartez gertatzen zela batipat eta neurri txikiago batean esnearekin. Esnearen bitartez emandako kanporaketa esporadikoa eta erditze ondorengo lehenengo hilabetean kontzentratua egongo litzateke, bestalde bagina zein gorotzen bidezko kanporaketa denboran luzeagoa litzateke. Gainera, erditze garaian zehar C. burnetii-ren kantitatea kuantifikatu zen, bai airean eta baita instalazioen barne nahiz kanpoaldean. Animalia sentibera nahiz esplotazioan sarri ibiltzen diren pertsonek, Q sukarraren transmisio arrisku altua zutela baieztatu zen. Bestalde, naturalki infektaturiko ardi-aziendengan txertoaren eraginkortasuna ikertzea planteatu zen. Txertoak emaitza onak eman zituen infektatu gabeko animalia sentiberak babesterakoan. Lau ardi-azienda ezberdin txertatu ziren eta bakoitzean, txertoaren efikazia baieztatzeko kontrol gisa jokatuko zuen txertatu gabeko talde bat aukeratu zen. Txertatu eta handik urte batera abortuen portzentaia jeitsi zela ikusi zen, baita animalia kanporatzaileen kopurua eta kanporatutako bakterio karga ere bai. Gainera, txertatu gabeko animaliengan serokonbertsioa gertatu zen. Honek, infekzio aktibo bat zegoela adierazten zuen eta txertoak nolabaiteko babes efekturen bat euki zezakeela pentsatu zen, animalia sentiberak babestuz. Hala ere, murrizpen hauek txertatu gabeko animaliengan ere ikusi ziren, naturalki gertatutako infekzioaren murrizpen bat denik ezin delarik baztertu, aurretik deskribatu den moduan. Txertoak epe laburrera efektu esanguratsurik ez zuela antzeman zen, ez bait zen ezberdintasun adierazgarririk ikusi animalia kanporatzaileen kopuruaren murrizpenean, ezta txertatutako zein kontrol gisa jokatzen zuten animalien arteko bakterioen kanporaketan. Horregatik txertoaren efikazia 4 urteren buruan ikertu zen infektaturiko ardi-azienda batengan. Lehenengo erditze garaian C. burnetii kanporatzen zuten animalien portzentaia altua zen, baina neurri handi batean portzentai hau murriztu zen txertatu eta handik bi urtetara, 3. eta 4. urteetan animalien eskrezioa desagertzera iritsi zelarik. Dena den, bakterioak ingurumenean egoten jarraitzen zuela baieztatu zen, 3. urtean zehar jasotako aerosolek eta txertoa jarri zen azken urtean, azalera solidoetan hartutako hauts laginak aztertu ondoren. Honela, gutxienez 5 urteren buruan txertoa jarri behar dela iradoki zen, C.burnetii-ren infekzioa ingurumenean maila baxuenetara murrizteko. Beraz, Euskal Autonomia Erkidego-an, C. burnetii etxeko ziklo nahiz basatian aurkitzen dela ondorioztatu dezakegu, ardi-azienda bakterio honen transmisio iturri garrantzitsua izanik. Gainera, basurde, orkatz, erbi eta hegaztia harrapakarien papera azpimarragarria da, gordailu gisa jokatu dezaketen einean. Ikerketa honek, informazio handia eskaintzen du ardi-azienda batengan Q sukarra-ren agerreraren aurrean, aurka egiteko kontrol estrategia ezberdinak eskainiz.