Clinical and epidemiological characteristics of Q fever in hospitalized patients

Retrospektivno su analizirane kliničke i epidemiološke značajke Q-groznice u 25 bolesnika koji su hospitalizirani u Klinici za infektivne bolesti u Zagrebu od 1. siječnja do 31. prosinca 2004. godine. Dijagnoza Q-groznice postavljena je u svih bolesnika serološki, imunoenzimskim testom (ELISA). Bolest se pojavljivala od ožujka do srpnja. Svi bolesnici su se razboljeli sporadično, a stanovnici su grada Zagreba i njegove okolice. Trinaest (52, 0%) bolesnika s Q-groznicom inficirano je u mjestu stanovanja, 10 (40, 0%) u drugim dijelovima Hrvatske, dok su dva (8, 0%) bolesnika u inkubacijskom razdoblju boravila u Bosni i Hercegovini. Bilo je znatno više muškaraca, nego žena (22:3). Većina bolesnika (68, 0%) je bila u dobi od 21-40 godina. Vodeći simptomi bolesti bili su vrućica, glavobolja i kašalj, a najvažniji patološki laboratorijski nalazi ubrzana sedimentacija eritrocita i povišena vrijednost C-reaktivnog proteina. Rendgenskim slikanjem pluća u većine bolesnika otkriven je intersticijski infiltrat, smješten u jednom plućnom režnju (23 ili 92, 0%). Pleuralni izljev je registriran u dva (8, 0%) bolesnika. Bolesnici su liječeni azitromicinom, fluorokinolonima i doksiciklinom. Doksiciklin je pokazao najbolji klinički učinak. Svi bolesnici su izliječeni.We retrospectively analysed clinical and epidemiological characteristics of Q fever in 25 patients hospitalized at the University Hospital for Infectious Diseases in Zagreb from January 1 to December 31, 2004. The diagnosis of Q fever was confirmed by serology in all patients, by an enzyme-linked immunosorbent assay (ELISA). The disease occurred from March to July. All patients were sporadic cases, and they were inhabitants of Zagreb and its surrounding areas. Thirteen (52.0 %) patients with Q fever were infected in their place of living, 10 (40.0 %) in other parts of Croatia, while 2 (8.0 %) patients were in Bosnia and Hercegovina during the incubation period. There were significantly more males than females (22:3). Most of the patients (68.0 %) were aged 21–40 years. Main symptoms of disease were fever, headache, and cough, and most significant pathological laboratory findings were accelerated erythrocyte sedimentation rate and increased value of C- reactive protein. Chest X-ray revealed interstitial pulmonary infiltrates in the majority of patients, localized in a single pulmonary lobe (23 or 92.0 %). Pleural effusion was recorded in 2 (8.0 %) patients. The patients were treated with azithromycin, fluoroquinolone, and doxycycline. Doxycycline showed the best clinical efficacy. All patients were cured

Clinical and epidemiological characteristics of Q fever in hospitalized patients

Retrospektivno su analizirane kliničke i epidemiološke značajke Q-groznice u 25 bolesnika koji su hospitalizirani u Klinici za infektivne bolesti u Zagrebu od 1. siječnja do 31. prosinca 2004. godine. Dijagnoza Q-groznice postavljena je u svih bolesnika serološki, imunoenzimskim testom (ELISA). Bolest se pojavljivala od ožujka do srpnja. Svi bolesnici su se razboljeli sporadično, a stanovnici su grada Zagreba i njegove okolice. Trinaest (52, 0%) bolesnika s Q-groznicom inficirano je u mjestu stanovanja, 10 (40, 0%) u drugim dijelovima Hrvatske, dok su dva (8, 0%) bolesnika u inkubacijskom razdoblju boravila u Bosni i Hercegovini. Bilo je znatno više muškaraca, nego žena (22:3). Većina bolesnika (68, 0%) je bila u dobi od 21-40 godina. Vodeći simptomi bolesti bili su vrućica, glavobolja i kašalj, a najvažniji patološki laboratorijski nalazi ubrzana sedimentacija eritrocita i povišena vrijednost C-reaktivnog proteina. Rendgenskim slikanjem pluća u većine bolesnika otkriven je intersticijski infiltrat, smješten u jednom plućnom režnju (23 ili 92, 0%). Pleuralni izljev je registriran u dva (8, 0%) bolesnika. Bolesnici su liječeni azitromicinom, fluorokinolonima i doksiciklinom. Doksiciklin je pokazao najbolji klinički učinak. Svi bolesnici su izliječeni.We retrospectively analysed clinical and epidemiological characteristics of Q fever in 25 patients hospitalized at the University Hospital for Infectious Diseases in Zagreb from January 1 to December 31, 2004. The diagnosis of Q fever was confirmed by serology in all patients, by an enzyme-linked immunosorbent assay (ELISA). The disease occurred from March to July. All patients were sporadic cases, and they were inhabitants of Zagreb and its surrounding areas. Thirteen (52.0 %) patients with Q fever were infected in their place of living, 10 (40.0 %) in other parts of Croatia, while 2 (8.0 %) patients were in Bosnia and Hercegovina during the incubation period. There were significantly more males than females (22:3). Most of the patients (68.0 %) were aged 21–40 years. Main symptoms of disease were fever, headache, and cough, and most significant pathological laboratory findings were accelerated erythrocyte sedimentation rate and increased value of C- reactive protein. Chest X-ray revealed interstitial pulmonary infiltrates in the majority of patients, localized in a single pulmonary lobe (23 or 92.0 %). Pleural effusion was recorded in 2 (8.0 %) patients. The patients were treated with azithromycin, fluoroquinolone, and doxycycline. Doxycycline showed the best clinical efficacy. All patients were cured

Difficulties in neuroborreliosis diagnostics

Neuroborelioza se može manifestirati različitim neurološkim poremećajima koje uzrokuju bakterije Borrelia burgdorferi sensu lato (s.l.). Kliničke manifestacije neuroborelioze nisu patognomonične. Etiološka dijagnoza neuroborelioze uglavnom se temelji na serološkim testovima i određivanju specifičnih protutijela za B. burgdorferi s.l. u likvoru. Fenotipske razlike vrsta B. burgdorferi s.l., razlike u njihovoj antigenoj strukturi, zemljopisnoj rasprostranjenosti te sposobnosti bolesnika za učinkovitu imunoreakciju određuju specifični humoralni odgovor. U dijelu bolesnika s neuroboreliozom protutijela se sintetiziraju samo intratekalno. Stoga je neophodno istovremeno testirati serum i likvor te odrediti indeks protutijela likvor/serum. U ovom radu analizirani su rezultati serološke dijagnostike 28 bolesnika s kliničkom dijagnozom neuroborelioze. Specifična protutijela IgM i IgG za B. burgdorferi s.l. određena su u serumu i likvoru rekombinantnim neizravnim imunoenzimskim testom (rELISA; Biomedica, Wien, Austria) te ELISA metodom »hvatanja« (engl. capture) za procjenu intratekalnih protutijela određivanjem indeksa protutijela (cELISA; IDEIALyme Neuroborreliosis, Dako, Denmark). Svi reaktivni rezultati u serumu potvrđeni su metodom Western blot (WB; Mikrogen, Germany or DPC Biermann GmbH, Germany). Specifični indeks protutijela u cELISA definiran je prema preporuci proizvođača. Intratekalna protutijela za B.burgdorferi s.l. dokazana su u 11 od 28 (39,3%) pacijenata pomoću cELISAi indeksa protutijela likvor/serum. Detektabilna protutijela u likvoru primjenom rELISA nađena su u 21 od 28 (75%) pacijenata. U 19 od 28 (67,9%) pacijenata rezultati rELISA potvrđeni su metodom WB. Sve serološke rezultate treba interpretirati u skladu s kliničkim i epidemiološkim podacima i koristiti ih za potvrdu kliničke dijagnoze, budući da serološki testovi za dokazivanje protutijela za B. burgdorferi nisu još standardizirani.Neuroborreliosis includes a variety of neurological disorders caused by Borrelia burgdorferi sensu lato. Clinical manifestation of neuroborreliosis is not pathognomonic. The etiological diagnosis is based mainly on serological tests and determination of specific anti-B. burgdorferi antibodies in cerebrospinal fluid (CSF). Specific antibodies response is influenced by phenotypic differences among B. burgdorferi species, different antigenic structure, their different geographic spreading, and patient\u27s possibility to react to infection. In some patients with neuroborreliosis antibodies could be produced only intrathecally. Therefore, it is always necessary to test serum and CSF simultaneously and determine the CSF/serum antibody index. In our study serological results of 28 patients with clinical diagnosis of neuroborreliosis were analyzed. Serum and CSF anti-B.burgdorferi IgM and IgG antibodies were determined by recombinant indirect ELISA (rELISA; Biomedica, Wien, Austria) and capture ELISA for intrathecal antibody synthesis detection by CSF/serum antibody index determination (cELISA; IDEIA Lyme Neuroborreliosis, Dako, Denmark). All sera positive results were confirmed by Western blot (WB; Mikrogen, (67,9 %) patients had confirmed rELISA results by WB. All serological results should be interpreted according to clinical and epidemiological data and used to confirm the clinical diagnosis, while serologic assays for anti-B. burgdorferi antibodies have not been standardized yet

Immunological response in Epstein-Barr virus infection

Epstein Barrov virus (EBV) je humani herpesvirus ubikvitaran u općoj populaciji. Poput drugih herpesvirusa ima latentnu i produktivnu fazu životnog ciklusa. U EBV-infekciji razvijaju se protutijela na različite antigene. Dijagnoza i definiranje statusa EBV-infekcije mogući su zbog karakterističnog odgovora specifičnih protutijela koja se mogu određivati komercijalno dostupnim testovima. U primarnoj infekciji počinju se stvarati protutijela IgM i IgG na virusni kapsidni antigen (VCA), detektiraju se protutijela na rane antigene (EA), a izostaju protutijela IgG za EBNA. Protutijela za EBNA i VCA pokazatelj su ranije EBV-infekcije. Reaktivaciju EBV obilježava visoki titar protutijela za EA, porast protutijela za VCA i ranija prisutnost protutijela za EBNA. Kontrola replikacije EBV primarno je posredovana citotoksičnim T-limfocitima i specifičnim protutijelima za EBV-antigene. Akutnu EBV-infekciju karakterizira samoograničavajuća proliferacija pomoćničkih CD4+ te poglavito citotoksičnih CD8+ T-limfocita. Citotoksični CD8+ T-limfociti uništavaju EBV-om zaražene B-limfocite i na taj način eliminiraju akutnu infekciju nakon čega slijedi doživotna latentna infekcija. Posljednjih se godina sve više istražuje EBV-specifična stanična imunost primjenom nove tehnologije MHC tetrametra. U akutnoj fazi EBV-infekcije dolazi do intenzivne proliferacije CD8+ T-limfocita specifičnih za litičke, ali i za latentne epitope ovog virusa. Određivanje EBV-specifične imunosti posebno je značajno za istraživanje patogeneze, ranu dijagnostiku te imunoterapiju post-transplantacijske limfoproliferativne bolesti.Epstein-Barr virus (EBV) is a human herpes virus that is ubiquitous in the adult population. Like all herpes viruses, EBV has latent and productive (lytic) phases in its life cycle. Infection with EBV induces the synthesis of antibodies to various virus antigens. A characteristic pattern of specific antibodies that can be determined by commercially-available assays enables the diagnosis and the definition of EBV profile in infected patients. In primary infection IgM and IgG antibodies to viral capsid antigen (VCA) start to produce; antibodies to early antigens (EA) are detectable; and antibodies to EBNA are not present. High anti-EA antibodies titre, anti-VCA titre rising and anti-EBNA antibodies predispose EBV reactivation. Cytotoxic T-cells and specific anti-EBV antibodies primarily mediate EBV replication control. Acute EBV-infection is characterized by a self-limiting proliferation of both helper-inducer CD4+ and cytotoxic- -suppressor CD8+ T-cells. The CD8+ T-cell immune response is believed to be responsible for the elimination of acute infection. Application of MHC tetramers demonstrated a massive expansion of CD8+ T-cells specific for both lytic and latent EBV proteins at the acute stage of infection. Characterisation of EBV-specific T-cells is an important experimental tool for the investigation of post-transplant lymphoproliferative disease pathogenesis and immunotherapy

Neuroretinitis associated with cat-scratch disease: a case report

U studenom 2003. godine u Centralnoj prijamnoj ambulanti Klinike za infektivne bolesti »Dr. Fran Mihaljević«, Zagreb liječena je bolesnica s vitritisom i stražnjim uveitisom oba oka te neuroretinitisom lijevog oka, nastalim tijekom bolesti mačjeg ogreba (BMO). Slabljenje vida nastalo je istovremeno s otokom limfnog čvora u aksili, tri tjedna nakon ogreba mačke. Nakon pregleda u jednoj zagrebačkoj klinici za očne bolesti, bolesnica je upućena u našu Kliniku radi etiološke dijagnostike i preporuke za antimikrobno liječenje. Idućeg dana hospitalizirana je na Klinici za očne bolesti. Za vrijeme hospitalizacije liječena je azitromicinom peroralno tijekom pet dana prema preporuci infektologa, uz lokalnu i parenteralnu terapiju kortikosteroidima. Bolest je imala povoljan ishod. Ovo je prvi slučaj neuroretinitisa nastalog tijekom BMO koji je dijagnosticiran u ovoj Klinici, u suradnji s oftalmolozima. Dijagnoza se temeljila na epidemiološkoj anamnezi, regionalnom limfadenitisu s odgovarajućim citološkim nalazom punktata i serološkoj potvrdi protutijela na Bartonellu henselae.In November 2003, a 32-year-old female patient with vitritis and uveitis (pars planitis) of both eyes and neuroretinitis of the left eye, associated with cat-scratch disease (CSD) was treated at the Central Admissions Department of the University Hospital for Infectious Diseases »Dr. Fran Mihaljevic«, Zagreb. Impaired vision occurred simultaneously with axillar lymph node swelling, three weeks after cat scratch. After the patient was examined at the Ophthalmology Clinic in Zagreb, she was referred to our Hospital for etiological diagnostics and recommendation for antimicrobial treatment. The following day the patient was hospitalized at the Ophthalmology Clinic. During hospitalization she was treated with azithromycin p.o. for five days according to recommendation by the infectious disease specialist, with local and parenteral corticosteroid therapy. The disease had favorable outcome. This is the first case of neuroretinitis associated with CSD that was diagnosed in our Hospital in collaboration with colleagues ophthalmologists. The diagnosis was based on epidemiological data, regional lymphadenitis with corresponding cytological finding and serological confirmation of antibodies to Bartonella henselae

Soluble FAS and transforming growth factor beta 2 in infections with viral and bacterial zoonoses

Određivali smo razine sFas (signalna receptor molekula koja biva otpuštena tijekom apoptoze u cirkulirajućem obliku) i TGF-β2 (multifunkcionalni citokin) u bolesnika s različitim zoonozama. Serumi su dobiveni od bolesnika hospitaliziranih u Klinici za infektivne bolesti »Dr. Fran Mihaljević«, Zagreb, Hrvatska, s dijagnozama: hemoragijska vrućica s bubrežnim sindromom – HVBS (n=20), leptospiroza (n=9), borelioza (n=7) ili krpeljni meningoencefalitis – KME (n=7). Za mjerenje razina sFas i TGF-β2 u serumima koristili smo ELISA kitove prema uputama proizvođača. Značajno povišena razina sFas je nađena u svih bolesnika. Ipak, bolesnici s KME ili boreliozom imali su značajno niže razine nego bolesnici s leptospirozom. Nasuprot tome, bolesnici s KME ili boreliozom su imali značajno više razine TGF-β2 nego zdrave kontrole. Naši preliminarni podaci ukazuju da bi povišene razine sFas i TGF-β2 mogle imati ulogu u imunopatogenezi ispitivanih virusnih i bakterijskih zoonoza.We determined levels of sFas (signal receptor molecule released during apoptosis in a soluble circulating form) and TGF-β2 (multifunctional cytokine) in patients with different zoonoses. Serum samples were obtained from patients hospitalized at the University Hospital for Infectious Diseases, Zagreb, Croatia with diagnoses of hemorrhagic fever with renal syndrome – HFRS, (n=20), leptospirosis (n=9), Lyme borreliosis (n=7), or tick-borne encephalitis – TBE (n=7). In all sera samples the levels of sFAS or TGF-β2 levels were measured using ELISAkits according to the manufacturer\u27s protocol. Significant increase in the levels of sFas was found in all patients. However, the patients with TBE or Lyme borreliosis had significantly lower levels than patients with leptospirosis. In contrary, patients with TBE or Lyme borreliosis had significantly higher levels of TGF-β2 than healthy controls. Our preliminary data indicate that an increase of sFas and TGF-β2 levels may have a role in the immunopathogenesis of tested viral and bacterial zoonoses

An outbreak of haemorrhagic fever with renal syndrome linked with mountain recreational activities in Zagreb, Croatia, 2017

Abstract In 2017 Zagreb faced the largest outbreak of haemorrhagic fever with renal syndrome (HFRS) to date. We investigated to describe the extent of the outbreak and identify risk factors for infection. We compared laboratory-confirmed cases of Hantavirus infection in Zagreb residents with the onset of illness after 1 January 2017, with individually matched controls from the same household or neighbourhood. We calculated adjusted matched odds ratios (amOR) using conditional logistic regression. During 2017, 104 cases were reported: 11–81 years old (median 37) and 71% (73) male. Compared with 104 controls, cases were more likely to report visiting Mount Medvednica (amOR 60, 95% CI 6–597), visiting a forest (amOR 46, 95% CI 4.7–450) and observing rodents (amOR 20, 95% CI 2.6–159). Seventy per cent of cases (73/104) had visited Mount Medvednica prior to infection. Among participants who had visited Mount Medvednica, cases were more likely to have drunk water from a spring (amOR 22, 95% CI 1.9–265), observed rodents (amOR 17, 95% CI 2–144), picked flowers (amOR 15, 95% CI 1.2–182) or cycled (amOR 14, 95% CI 1.6–135). Our study indicated that recreational activity around Mount Medvednica was associated with HFRS. We recommend enhanced surveillance of the recreational areas during an outbreak