Introduction: Vaccination against varicella rapidly reduces disease incidence, resulting in reductions in both individual burden and societal costs. Despite these benefits, there is no ...standardization of varicella immunization policies in Europe, including countries in Central and Eastern Europe (CEE).
Areas covered: This systematic literature review identified publications on the epidemiology of varicella, its associated health and economic burden, and vaccination strategies within the CEE region, defined as Albania, Bosnia-Herzegovina, Bulgaria, Croatia, Cyprus, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Serbia, Slovakia, and Slovenia. Twenty-six studies were identified from a search of PubMed, Embase®, and MEDLINE® biomedical literature databases, supplemented by gray literature and country-specific/global websites.
Expert commentary: Limited information exists in published studies on the burden of varicella in CEE. The wide variability in incidence rates between countries is likely explained by a lack of consistency in reporting systems. Funded universal varicella vaccination (UVV) in CEE is currently available only in Latvia as a one-dose schedule, but Hungary together with Latvia are introducing a two-dose strategy in 2019. For countries that do not provide UVV, introduction of vaccination is predicted to provide substantial reductions in cases and rates of associated complications, with important economic benefits.
Alergenska imunoterapija (AIT) još uvijek je jedina dostupna terapija alergijskih bolesti koja djeluje na imunosnu disfunkciju u podlozi alergije te može modificirati tijek i napredovanje bolesti. ...Suvremeno načelo imunoterapije ne razlikuje se znatnije od ideje koju je imao Leonard Noon 1911. godine, kad je prvi puta AIT primijenjena za liječenje alergijskog rinitisa. AIT podrazumijeva ponavljanu primjenu rastućih doza alergena supkutanim injekcijama do doze održavanja koja se primjenjuje tijekom najmanje tri godine, čime se postiže specifična tolerancija na alergen s dugoročnom učinkovitošću i nakon prekida liječenja. U novije vrijeme sublingvalni put primjene, provediv i u kućnim uvjetima, pokazao se učinkovitom i sigurnom alternativom supkutanom putu. Oralna se imunoterapija sve više primjenjuje u liječenju IgE posredovane alergije na hranu i omogućava postizanje učinkovite ograničene desenzitizacije, ali ne i dugotrajne tolerancije. Imunosni mehanizmi pojave tolerancije uključuju povećano stvaranje interleukina 10 (IL-10) i transformirajućeg faktora rasta beta (TGF-β), smanjenje broja alergenski specifičnih T-pomoćničkih stanica tipa 2 (Th2), indukciju alergenski specifičnih regulacijskih limfocita T i B (Tregs i Bregs) i proizvodnju alergenski specifičnih IgG 4 i IgA blokirajućih protutijela. S obzirom na stalan porast prevalencije alergijskih bolesti, od velikog je interesa u liječenju alergija istražiti nove metode za postizanje imunotolerancije sa sigurnijim, učinkovitijim i dugotrajnijim učinkom; to uključuje alternativne putove primjene alergena za imunoterapiju, nove adjuvanse, rekombinantne alergene (uključujući hipoalergene varijante) i kombinaciju alergena s imunološkim modifikatorima ili monoklonskim protutijelima koji potiskuju Th2 stanični put.
The major characteristic of asthma is persistent airway inflammation that fails to resolve spontaneously. Dysregulation of pro- and anti-inflammatory mechanisms is responsible for the development of ...chronic inflammation. The inflammatory reaction is mediated by numerous cells and their mediators. Detection and quantification of airway inflammation in children are subject to many requirements, e.g., use of biologic samples obtained in a non-invasive way; use of standardized analytical methods to determine biomarkers that can identify inflammation processes (inflammation itself, oxidative stress, apoptosis and remodelling); determining the role of systemic inflammation; assessment of correlation of various biomarkers of inflammation with clinical parameters and their diagnostic efficacy; providing a tool(s) to monitor diseases, and to evaluate adequacy of therapy; and predicting the clinical course of inflammation and prognosis of asthma. Using standardized analyses, it is now possible to determine direct markers of local inflammation, i.e., fractional nitric oxide (marker of oxidative stress) in exhaled breath, pH (marker of acid stress) in breath condensate, and indirect markers in blood/serum, i.e., eosinophil granulocytes (indicating migration), eosinophil cationic protein (marker of activated eosinophil granulocytes) and C-reactive protein (marker of systemic inflammation). However, none of these biomarkers are specific for asthma. Further standardization of the known pulmonary biomarkers of local inflammation and identification of new ones will allow for longitudinal follow-up of inflammation in children with asthma.
Primary immunodeficiency disorders are a recognized public health problem worldwide. The prototype of these conditions is X-linked agammaglobulinemia (XLA) or Bruton's disease. XLA is caused by ...mutations in Bruton's tyrosine kinase gene (BTK), preventing B cell development and resulting in the almost total absence of serum immunoglobulins. The genetic profile and prevalence of XLA have not previously been studied in Eastern and Central European (ECE) countries. We studied the genetic and demographic features of XLA in Belarus, Croatia Hungary, Poland, Republic of Macedonia, Romania, Russia, Serbia, Slovenia, and Ukraine. We collected clinical, immunological, and genetic information for 122 patients from 109 families. The BTK gene was sequenced from the genomic DNA of patients with a high susceptibility to infection, almost no CD19(+) peripheral blood B cells, and low or undetectable levels of serum immunoglobulins M, G, and A, compatible with a clinical and immunological diagnosis of XLA. BTK sequence analysis revealed 98 different mutations, 46 of which are reported for the first time here. The mutations included single nucleotide changes in the coding exons (35 missense and 17 nonsense), 23 splicing defects, 13 small deletions, 7 large deletions, and 3 insertions. The mutations were scattered throughout the BTK gene and most frequently concerned the SH1 domain; no missense mutation was detected in the SH3 domain. The prevalence of XLA in ECE countries (total population 145,530,870) was found to be 1 per 1,399,000 individuals. This report provides the first comprehensive overview of the molecular genetic and demographic features of XLA in Eastern and Central Europe.
Sažetak. Ovaj pregledni članak o gripi (influenci) sadržava mikrobiološke, imunološke i epidemiološke podatke posljednjih 10 godina kako bi liječnicima omogućio lakše snalaženje u argumentima za ...izbor vlastitog cijepljenja. Ukratko se prelaze osnove mikrobiologije virusa influence, njegove patogeneze i širenja. Raspravlja se o razlozima antigenske nepodudarnosti cjepnih i divljih sojeva, uključujući i one tehnološko-proizvodne prirode. Tablično se izlaže usporedba epidemioloških i vakcinalnih parametara sezonske gripe u posljednjih 10 godina. Udio A-podtipova i B-tipova (loza) virusa influence, antigenska podudarnost i prosječna zaštitnost cjepiva izdvojeni su iz podataka Centers for Disease Control and Prevention, SAD i Hrvatskog zavoda za javno zdravstvo. Pokazalo se da od 2010. g. raste udio drugog B-virusa u sezonskoj gripi. Sve se više preporučuju četverovalentna cjepiva koja uključuju 2 A-podtipa i 2 B-loze. Neizravni podatci koji su izronili tijekom pandemije H1N1 2009. g. pokazuju da imunost, prema specifičnom podtipu influence, može biti znatno dugotrajnija od jedne sezone. Širu, ali slabije specifičnu zaštitu može pružiti imunost prema heterosuptipskim antigenima prisutnim u unutrašnjosti viriona koja se stječe prirodnom infekcijom. U cjepiva tekuće sezone, a prema predviđanju Svjetske zdravstvene organizacije, uvrštena su kao najvjerojatnije dominantna ova 4 soja: A/Michigan, A/Singapore, B/Colorado i B/Phuket. Od ovih je A/Michigan varijanta pandemijskog virusa iz 2009. g. (A/California/07/2009), a A/Singapore i B/Colorado novi su sojevi kojih nije bilo u cjepivima prethodnih sezona. B/Phuket nalazio se u trovalentnom cjepivu u sezoni 2015. – 2016. g. i u četverovalentnom cjepivu u sezonama 2016. – 2017. i 2017. – 2018. Osobe koje se nisu cijepile 2014. – 2015. g. trebale bi ove sezone posegnuti za četverovalentnim cjepivom, dok bi onima koji su se cijepili trovalentnim cjepivom 2015. – 2016. g. ili četverovalentnim cjepivom 2016. – 2017. g. i/ili 2017. – 2018. g. trovalentno cjepivo u ovoj sezoni trebalo biti dovoljno.
To gain insight into the peculiarities of clinical presentation and time of diagnosis in the population of patients with combined immunodeficiency treated in our center.We retrospectively analyzed 22 ...patients with combined immunodeficiency treated in our center in the past 25 years. Clinical findings were collected, including age of presentation and age of diagnosis, genetic defects, consanguinity, family history, number and site of infections, presence of diarrhea, failure to thrive, skin rash, vaccine complications and type of treatment. Immunological findings included WBC with absolute counts, lymphocyte subsets and immunoglobulin levels.Patients (n=22) with severe combined immunodeficiency (n=17) and other combined immunodeficiencies (n=5) were included in the study. Sixteen patients (77%) were male. The most common clinical manifestations were opportunistic infections. Most of the patients were diagnosed after 3 months of age. Prenatal diagnosis was performed in one patient (4.5%), two patients(9%) did not undergo genetic analysis. The spectrum of genetic defect in our cohort show wide heterogeneity. Seventeen patients (77%) underwent HSCT, one patient (4.5%) is on enzyme replacement therapy. None of our patients have undergone gene therapy. Twelve patients (54.5%) died, of which four (18%) died before HSCT.Combined immunodeficiencies are fatal without definitive therapy (HSCT or gene therapy). The outcomes are better if infants are diagnosed and treated in pre-symptomatic stage, preferably before 3.5 months of age. More and more countries are implementing newborn screening for primary immunodeficiency diseases in their health care systems to diagnose patients as early as possible and to prevent infections. For the same reason, we advocate for expanding our national neonatal screening program
Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 ...kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guérin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years ± 9.8 years (range, 0.5-46.4 yr). IL-12Rβ1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought.
Interleukin-12 receptor beta 1 (IL-12R beta 1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients ...from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guerin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years +/- 9.8 years (range, 0.5-46.4 yr). IL-12R beta 1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought.
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