Specific immunotherapy

Alergen specifična imunoterapija uspješno se primjenjuje u pacijenata s alergijskim bolestima više od sto godina. Iako efikasan oblik liječenja, uz ovaj tip terapije povezan je i rizik od neželjenih reakcija posredovanih IgE antitijelima, uključujući sistemsku anafilaksiju. Postupak se temelji na činjenici da će organizam koji je redovito izložen antigenu razviti toleranciju na taj alergen. Uspješnost specifične imunoterapije počiva na modulaciji antigen specifičnih reakcija organizma. Pod modulacijom podrazumijevamo relativno smanjenje imunološkog odgovora posredovanog limfocitima Th2 te povećanje parametara pripisivih reakcijama limfocita Th1. Regulacijski limfociti (Treg) prepoznati su kao ključne stanice koje vrše supresiju imunološkog odgovora. Podvrste limfociti Treg, Tr1 i FoxP3+ limfociti luče velike količine interleukina 10 (IL-10) čiji su glavni učinci 1) aktivacija stanica sličnih Tr1 (Tr1- like), 2) nepotpuna diferencijacija dendritičkih stanica koje posljedično tome postaju tolerogene i 3) izotipsko prekapčanje u limfocitima B koji počinju proizvoditi specifični imunoglobulin IgG4 umjesto imunoglobulina IgE. Tr1-like stanice proizvode drugi važan citokin, TGF-β, u čijem prisustvu novonastale tolerogene dendritičke stanice utječu na povećano stvaranje i akumulaciju Tr1 i Tr1-like stanica osiguravajući daljnju proizvodnju IL- 10. Rezultat izotipskog prekapčanja u limfocitima B je povećan omjer IgE/IgG4. IgG4 protutijela su specifična za iste epitope na antigenu kao i IgE, te time suprimiraju alergijsku reakciju na dva načina. Blokiranjem vezanja antigena za BCR receptor na limfocitima B zaustavljaju proizvodnju IgE protutijela, a s druge strane onemogućuju vezanje antigena na FcƐR i FcƐRII receptore na efektorskim stanicama koje izlučuju medijatore (mastociti, bazofili, eozinofili). Za razliku od simptomatske terapije, specifična imunoterapija predstavlja optimalan oblik liječenja alergijskih bolesti koji djeluje na sam nastanak bolesti i uzrokuje dugotrajnu kliničku remisiju.Patients with allergic diseases have been successfully treated with allergen-specific immunotherapy for over a hundred years. Although it is an efficient form of treatment, this type of therapy is also associated with the risk of unwanted reactions caused by IgE antibodies, including systemic anaphylaxis. The treatment is based on the fact that the organism which is regularly exposed to the antigene will develop tolerance to that antigene. The success of specific immunotherapy rests on the modulation of antigene-specific reactions of the organism. By modulation it is meant a relative weakening of the immune response caused by Th2 lymphocytes and the increase of parameters associated with the Th1 lymphocyte reations. Regulation lympphocytes (Treg) are recognized as key cells which suppress the immunological response. Subytpes Treg, Tr1 lymphocytes and FoxP3+ lymphocytes secrete large amounts of interleukin 10 (IL-10) whose main effects include 1) activation of Tr1-like cells, 2) incomplete differentiation of dendritic cells which consequentially become tolerogenic, and 3) isotype chnge in B lymphocytes which start producing specific immunoglobulin IgG4 instead of immunoglobulin IgE. Tr1-like cells produce another important cytokine, TGF-β, in whose presence the newly produced tolerogenic dendritic cells affect the increased production and accumulation of Tr1 and Tr1- like cells, thus ensuring further production IL-10. Isotypical change in B lymphocytes results in an increased ratio of IgE/IgG4. IgG4 antibodies are specific for the same epitope on the antigene as the IgE, and they suppress allergic reaction in two ways. On one hand, by blocking the attachment of antigenes to the BCR receptor on B lymphocytes they stop the production of IgE antibodies, and on the other hand they disable the attachment of antigenes to FcƐR iandFcƐRII receptors on effector cells which secrete mediators (mastocytes, basophils, eosinophils). Unlike symptomatic therapy, specific immunotherapy represents the optimal type of treatment of allergic diseases that affects the disease ethiologically and causes long-term clinical remission

The Role of Mosquito Surveillance in Monitoring Arboviral Infections in Croatia

U skladu s uočenim trendom porasta broja slučajeva zaraznih bolesti koje se prenose vektorima, dolazi do povećanja razmjera javnozdravstvenog problema, no s druge strane i do jačanja kapaciteta u svrhu suzbijanja navedenih bolesti. S ciljem zaštite populacije od arbovirusnih infekcija nameće se potreba za kontinuiranom provedbom praćenja i procjenom rizika utjecaja vektora i vektorskih bolesti na zdravlje, za što je neophodno prikupljanje podataka kroz programe praćenja. U problematici zaraznih bolesti koje se prenose vektorima potrebno je integrirano obuhvatiti aktivnosti koje se odnose na nadzor nad vektorima, entomološke djelatnosti, sustav ranog otkrivanja, preventivno suzbijanje, protuepidemijske mjere te praćenja prisutnosti virusa u vektorima, rezervoarima ili zaraženim životinjama. U Hrvatskoj je zakonom propisano praćenje komaraca na lokalnoj i na državnoj razini te je na inicijativu Hrvatskog zavoda za javno zdravstvo uspostavljen monitoring invazivnih vrsta komaraca koji se kontinuirano provodi od 2016. godine.In accordance with the noticed growing trend in the number of vector-borne disease cases, the extent of public health significance of this problem is also increasing. However, the strengthening of capacities for suppression of these outbreaks is present. With the aim of protecting population from arbovirus infections, there is a need for continuous monitoring and evaluation of risk factors related to vectors and vector borne diseases and human health, for which data is acquired through monitoring programs. In order to address these issues, several activities must be integrated and taken into consideration: vector surveillance, entomological activity, early detection system, preventive measures, counter-epidemic measures and virus detection in vectors, reservoirs or infected animals. There is a legal framework regarding mosquito monitoring on a local, as well as national level. Additionally, at the initiative of the Croatian Institute of Public Health, invasive mosquito species monitoring is being implemented and continuously conducted since 2016

Specific immunotherapy

Alergen specifična imunoterapija uspješno se primjenjuje u pacijenata s alergijskim bolestima više od sto godina. Iako efikasan oblik liječenja, uz ovaj tip terapije povezan je i rizik od neželjenih reakcija posredovanih IgE antitijelima, uključujući sistemsku anafilaksiju. Postupak se temelji na činjenici da će organizam koji je redovito izložen antigenu razviti toleranciju na taj alergen. Uspješnost specifične imunoterapije počiva na modulaciji antigen specifičnih reakcija organizma. Pod modulacijom podrazumijevamo relativno smanjenje imunološkog odgovora posredovanog limfocitima Th2 te povećanje parametara pripisivih reakcijama limfocita Th1. Regulacijski limfociti (Treg) prepoznati su kao ključne stanice koje vrše supresiju imunološkog odgovora. Podvrste limfociti Treg, Tr1 i FoxP3+ limfociti luče velike količine interleukina 10 (IL-10) čiji su glavni učinci 1) aktivacija stanica sličnih Tr1 (Tr1- like), 2) nepotpuna diferencijacija dendritičkih stanica koje posljedično tome postaju tolerogene i 3) izotipsko prekapčanje u limfocitima B koji počinju proizvoditi specifični imunoglobulin IgG4 umjesto imunoglobulina IgE. Tr1-like stanice proizvode drugi važan citokin, TGF-β, u čijem prisustvu novonastale tolerogene dendritičke stanice utječu na povećano stvaranje i akumulaciju Tr1 i Tr1-like stanica osiguravajući daljnju proizvodnju IL- 10. Rezultat izotipskog prekapčanja u limfocitima B je povećan omjer IgE/IgG4. IgG4 protutijela su specifična za iste epitope na antigenu kao i IgE, te time suprimiraju alergijsku reakciju na dva načina. Blokiranjem vezanja antigena za BCR receptor na limfocitima B zaustavljaju proizvodnju IgE protutijela, a s druge strane onemogućuju vezanje antigena na FcƐR i FcƐRII receptore na efektorskim stanicama koje izlučuju medijatore (mastociti, bazofili, eozinofili). Za razliku od simptomatske terapije, specifična imunoterapija predstavlja optimalan oblik liječenja alergijskih bolesti koji djeluje na sam nastanak bolesti i uzrokuje dugotrajnu kliničku remisiju.Patients with allergic diseases have been successfully treated with allergen-specific immunotherapy for over a hundred years. Although it is an efficient form of treatment, this type of therapy is also associated with the risk of unwanted reactions caused by IgE antibodies, including systemic anaphylaxis. The treatment is based on the fact that the organism which is regularly exposed to the antigene will develop tolerance to that antigene. The success of specific immunotherapy rests on the modulation of antigene-specific reactions of the organism. By modulation it is meant a relative weakening of the immune response caused by Th2 lymphocytes and the increase of parameters associated with the Th1 lymphocyte reations. Regulation lympphocytes (Treg) are recognized as key cells which suppress the immunological response. Subytpes Treg, Tr1 lymphocytes and FoxP3+ lymphocytes secrete large amounts of interleukin 10 (IL-10) whose main effects include 1) activation of Tr1-like cells, 2) incomplete differentiation of dendritic cells which consequentially become tolerogenic, and 3) isotype chnge in B lymphocytes which start producing specific immunoglobulin IgG4 instead of immunoglobulin IgE. Tr1-like cells produce another important cytokine, TGF-β, in whose presence the newly produced tolerogenic dendritic cells affect the increased production and accumulation of Tr1 and Tr1- like cells, thus ensuring further production IL-10. Isotypical change in B lymphocytes results in an increased ratio of IgE/IgG4. IgG4 antibodies are specific for the same epitope on the antigene as the IgE, and they suppress allergic reaction in two ways. On one hand, by blocking the attachment of antigenes to the BCR receptor on B lymphocytes they stop the production of IgE antibodies, and on the other hand they disable the attachment of antigenes to FcƐR iandFcƐRII receptors on effector cells which secrete mediators (mastocytes, basophils, eosinophils). Unlike symptomatic therapy, specific immunotherapy represents the optimal type of treatment of allergic diseases that affects the disease ethiologically and causes long-term clinical remission

Divergent Trends in the Prevalence of Children’s Asthma, Rhinitis and Atopic Dermatitis and Environmental Influences in the Urban Setting of Zagreb, Croatia

Background: Previous studies have reported that the allergy epidemic in developed countries has reached its plateau, while a rise is expected in developing ones. Our aim was to compare the prevalence of allergic diseases among schoolchildren from the city of Zagreb, Croatia after sixteen years. Methods: Symptoms of asthma, allergic rhinitis (AR) and atopic dermatitis (AD) and risk factors were assessed using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. An allergic profile was determined by a skin prick test. Results: The prevalence of current, ever-in-a-lifetime and diagnosed AR of 35.7%, 42.5% and 14.9% and AD of 18.1%, 37.1% and 31.1% demonstrated a significant increase. The asthma prevalence has remained unchanged. The allergen sensitivity rate has remained similar, but pollens have become dominant. Mould and dog exposure are risks for asthma (OR 14.505, OR 2.033). Exposure to cat allergens is protective in AR (OR 0.277). Parental history of allergies is a risk factor in all conditions. Conclusion: Over sixteen years, the prevalence of AR and AD, but not of asthma, have increased. The proportion of atopy has remained high. The AR/AD symptom rise is probably a consequence of increased pollen sensitisation united with high particulate matter concentrations. The stable asthma trend could be a result of decreasing exposures to indoor allergens

SARS-CoV-2 Seroprevalence and Neutralizing Antibody Response after the First and Second COVID-19 Pandemic Wave in Croatia

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus with a pandemic spread. So far, a total of 349,910 SARS-CoV-2 cases and 7687 deaths were reported in Croatia. We analyzed the seroprevalence and neutralizing (NT) antibody response in the Croatian general population after the first (May–July 2020) and second (December 2020–February 2021) pandemic wave. Initial serological testing was performed using a commercial ELISA, with confirmation of reactive samples by a virus neutralization test (VNT). A significant difference in the overall seroprevalence rate was found after the first (ELISA 2.2%, VNT 0.2%) and second waves (ELISA 25.1%, VNT 18.7%). Seropositive individuals were detected in all age groups, with significant differences according to age. The lowest prevalence of NT antibodies was documented in the youngest (<10 years; 16.1%) and the oldest (60–69/70+ years; 16.0% and 12.8%, respectively) age groups. However, these age groups showed the highest median NT titers (32–64). In other groups, seropositivity varied from 19.3% to 21.5%. A significant weak positive correlation between binding antibody level as detected by ELISA and VNT titer (rho = 0.439, p < 0.001) was observed. SARS-CoV-2 NT antibody titers seem to be age-related, with the highest NT activity in children under 10 years and individuals above 50 years

The Emergence of SARS-CoV-2 within the Dog Population in Croatia: Host Factors and Clinical Outcome

Over a year into the COVID-19 pandemic, there is growing evidence that SARS-CoV-2 infections among dogs are more common than previously thought. In this study, the prevalence of SARS-CoV-2 antibodies was investigated in two dog populations. The first group was comprised of 1069 dogs admitted to the Veterinary Teaching Hospital for any given reason. The second group included dogs that shared households with confirmed COVID-19 cases in humans. This study group numbered 78 dogs. In COVID-19 infected households, 43.9% tested ELISA positive, and neutralising antibodies were detected in 25.64% of dogs. Those data are comparable with the secondary attack rate in the human population. With 14.69% of dogs in the general population testing ELISA positive, there was a surge of SARS-CoV-2 infections within the dog population amid the second wave of the pandemic. Noticeably seroprevalence of SARS-CoV-2 in the dog and the human population did not differ at the end of the study period. Male sex, breed and age were identified as significant risk factors. This study gives strong evidence that while acute dog infections are mostly asymptomatic, they can pose a significant risk to dog health. Due to the retrospective nature of this study, samples for viral isolation and PCR were unavailable. Still, seropositive dogs had a 1.97 times greater risk for developing central nervous symptoms