Goran Tešović

Central European Vaccination Advisory Group (CEVAG) guidance statement on recommendations for influenza vaccination in children

BackgroundInfluenza vaccination in infants and children with existing health complications is current practice in many countries, but healthy children are also susceptible to influenza, sometimes with complications. The under-recognised burden of disease in young children is greater than in elderly populations and the number of paediatric influenza cases reported does not reflect the actual frequency of influenza.DiscussionVaccination of healthy children is not widespread in Europe despite clear demonstration of the benefits of vaccination in reducing the large health and economic burden of influenza. Universal vaccination of infants and children also provides indirect protection in other high-risk groups in the community. This paper contains the Central European Vaccination Advisory Group (CEVAG) guidance statement on recommendations for the vaccination of infants and children against influenza. The aim of CEVAG is to encourage the efficient and safe use of vaccines to prevent and control infectious diseases.SummaryCEVAG recommends the introduction of universal influenza vaccination for all children from the age of 6 months. Special attention is needed for children up to 60 months of age as they are at greatest risk. Individual countries should decide on how best to implement this recommendation based on their circumstances.

Recommendations for tick-borne encephalitis vaccination from the Central European Vaccination Awareness Group (CEVAG).

Tick-borne encephalitis (TBE) is a viral neurological zoonotic disease transmitted to humans by ticks or by consumption of unpasteurized dairy products from infected cows, goats, or sheep. TBE is highly endemic in areas of Central and Eastern Europe and Russia where it is a major public health concern. However, it is difficult to diagnose TBE as clinical manifestations tend to be relatively nonspecific and a standardized case definition does not exist across the region. TBE is becoming more important in Europe due to the appearance of new endemic areas. Few Central European Vaccination Awareness Group (CEVAG) member countries have implemented universal vaccination programmes against TBE and vaccination coverage is not considered sufficient to control the disease. When implemented, immunization strategies only apply to risk groups under certain conditions, with no harmonized recommendations available to date across the region. Effective vaccination programmes are essential in preventing the burden of TBE. This review examines the current situation of TBE in CEVAG countries and contains recommendations for the vaccination of children and high-risk groups. For countries at very high risk of TBE infections, CEVAG strongly recommends the introduction of universal TBE vaccination in children > 1 y of age onwards. For countries with a very low risk of TBE, recommendations should only apply to those traveling to endemic areas. Overall, it is generally accepted that each country should be free to make its own decision based on regional epidemiological data and the vaccination calendar, although recommendations should be made, especially for those living in endemic areas.

Concentration gradient of CXCL10 and CXCL11 between the cerebrospinal fluid and plasma in children with enteroviral aseptic meningitis

BACKGROUND Lymphocyte migration from the blood into the CNS is mediated by chemokines and chemokine receptors. Chemokines CXCL10 and CXCL11 are important for the recruitment of CXCR3-expressing Th1 lymphocytes to the site of inflammation. AIMS To determine the concentrations of CXCL10 and CXCL11 in the CSF and plasma of children with enteroviral aseptic meningitis (EV AM) and controls and the contribution of these chemokines to the chemokine concentration gradient between the periphery and the CNS. METHODS The study included 26 pediatric patients with EV AM and 16 controls in whom CNS infection is excluded by negative CSF examination. Chemokines were quantified by using enzyme immunoassay. Etiological diagnosis of EV AM was based on the detection of enteroviral RNA in the CSF using real-time PCR. RESULTS CXCL10 (median 12 725 pg/ml) and CXCL11 (median 187 pg/ml) concentrations in CSF of patients with meningitis were significantly higher compared to plasma (median 173 pg/ml and median 110 pg/ml; p < 0.001, p = 0.026 respectively). CXCL10 concentrations in the CSF (median 198 pg/ml) and plasma of controls (median 124 pg/ml) were not significantly different (p = 0.642). CXCL11 concentrations in the CSF of controls (median 89 pg/ml) were significantly lower compared with plasma (median 139 pg/ml, p = 0.004). Chemokine concentration gradient was not influenced by pleocytosis, nor dependent on cytologic CSF formula or the presence of proteinorrachia. CONCLUSION CXCL10 and CXCL11 concentration gradient between the CSF and plasma in children with EV AM suggests an important role of these chemokines in the T-cells recruitment into the CNS and local immunoreaction.

Rubella revisited: where are we on the road to disease elimination in Central Europe?

Rubella is a contagious viral disease with few complications except when contracted by pregnant women. Rubella infection in pregnancy can result in miscarriage, stillbirth or an infant born with congenital rubella syndrome (CRS) which comprises deafness, heart disease, cataracts and other permanent congenital manifestations. Clinical diagnosis of rubella is difficult due to overlapping symptoms with many other diseases and confirmation of rubella is not possible without laboratory testing. Effective vaccination programmes are critical to the elimination of rubella and prevention of CRS. Such programmes have been successful in several countries in Europe and around the world. However, rubella outbreaks still occur due to suboptimal vaccine coverage and in the past 10 years rubella has been reported in Central European countries such as Romania and Poland. Over the past decade the elimination of rubella and prevention of congenital rubella infection in Europe has been a high priority for the WHO European Regional Office. In 2010 the WHO regional committee for Europe renewed its commitment to the elimination of rubella and prevention of CRS with a new target of 2015. This paper examines the current situation for rubella and CRS in Central Europe and describes the different rubella vaccination programmes in the region. The Central European Vaccination Advisory Group (CEVAG) recommends that two doses of measles, mumps and rubella vaccine, MMR, should be given to all children. The first dose should be given between 12 and 15 months of age. The second dose can be given between the ages of 21 months and 13 years with the exact age of administration of the second dose depending on the situation specific to each country. All suspected rubella cases should be laboratory-confirmed and monitoring systems to detect and investigate cases of CRS should be strengthened.

Analysis of biennial outbreak pattern of respiratory syncytial virus according to subtype (A and B) in the Zagreb region

Background:  The epidemic pattern of respiratory syncytial virus (RSV) in Croatia is biennial. In order to determine if the circulation of different RSV subtypes affects the outbreak cycle, the aim of the present study was to analyze the epidemic pattern of RSV in children in Croatia (Zagreb region) over a period of 3 consecutive years.

Rotavirus vaccination in central Europe.

Each year, rotavirus (RV) infection is the leading cause of acute gastroenteritis requiring hospitalisation and of nosocomially transmitted diseases in children younger than 5 years across Central European Vaccination Awareness Group (CEVAG) countries; however, inadequate surveillance systems and lack of routine RV testing still exist in most CEVAG countries, making it difficult to accurately assess the present burden of acute RV gastroenteritis in the younger population. Furthermore, routine immunisation of infants with RV vaccines has not been implemented, and no official and uniform recommendations exist in most of the countries in these territories. The present study provides CEVAG country-specific estimates of the disease burden of RV gastroenteritis among the youngest population and presents evidence-based advice on the use of RV vaccines in the region, while providing a framework for vaccination at the national level.

Seasonal occurrence of human metapneumovirus infections in Croatia.

Background: Human metapneumovirus (HMPV) is 1 of the commonest causes of viral ARI especially among pediatric patients. Its incidence varies from year to year in countries belonging to moderate climate zone. The aim of this study was to investigate epidemiologic characteristics of HMPV infections in Croatia. Methods: During a 4-year period (January 1, 2009, through December 31, 2012), nasopharyngeal aspirates were collected from 2610 children <10 years who were admitted to hospitals with acute respiratory infections. Direct immunofluorescence assay was used to detect the virus from clinical samples. Demographics and clinical data were also analyzed. Results: HMPV was detected in 8.4% of patients. While many of HMPV-infected children were 13–24 months of age (30.9% of all proven HMPV infections), the highest incidence of HMPV infection was recorded in 2- to 5-year-old children (11.4% of all children in this age group). HMPV caused 7.1% of upper respiratory tract infections and 11.7% of lower respiratory tract infections. Annual prevalence rates of HMPV infection varied significantly from year to year (P < 0.001). Peak incidence was detected in spring or winter months, depending on the year. Conclusions: This study indicates that HMPV infections in Croatia show a biennial outbreak pattern characterized by alternation of winter and spring activity. HMPV outbreaks alternate with respiratory syncytial virus outbreaks.

Herpes simplex primo-infection in an immunocompetent host with eosinophilic esophagitis.

Eosinophilic esophagitis and herpes simplex esophagitis are separately well‐described entities, but their simultaneous occurrence may pose a special challenge to the clinician, especially regarding the optimal therapeutic approach. The following case report describes a patient with a history of cows milk and dairy products intolerance, but without an underlying immunologic defect, in whom eosinophilic esophagitis was diagnosed in the course of primary herpes simplex virus 1 (HSV1) infection that clinically presented as herpes labialis and severe esophagitis. The diagnosis was confirmed by a polymerase chain reaction from cytological brush and by immunohistochemical staining that detected the presence of HSV1 DNA in esophageal mucosa, and histologically by persistent eosinophil‐predominant inflammation, typical of eosinophilic esophagitis. Despite severe clinical presentation, the HSV1 infection was self‐limited. After a directed elimination diet was introduced, the clinical course was favorable, without the need for antiviral therapy.

Adult vaccination in 11 Central European countries - calendars are not just for children.

As Europes population ages, disease morbidity and treatment costs in the adult population are likely to rise substantially, making this a pertinent time to review and revise preventive strategies such as vaccination. Vaccine uptake remains a problem for adults and there is a lack of coordinated programmes for vaccination of adults. Countries in Western Europe have begun to identify the need to increase adult vaccination, but the situation in Central European countries remains poorly identified and inadequately described. This paper summarises the evidence to support the development of an adult vaccination calendar in the Central European Vaccination Awareness Group (CEVAG) member countries (Bulgaria, Croatia, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Romania, Slovakia, Slovenia and Turkey). CEVAG recommends the introduction of an adult vaccination calendar, which should include vaccination against diseases that represent a large burden in adults in terms of mortality and morbidity. This calendar could be modified to meet the priorities of individual countries.

Unusually difficult clinical presentation of an infant suffering from congenital Cytomegalovirus (CMV) infection combined with alpha 1-antitrypsin (A1AT) deficiency.

Congenital Cytomegalovirus (CMV) infection and alpha 1-antitrypsin (A1AT) deficiency are separately well described entities, but their simultaneous occurrence can pose a special challenge to a clinician, especially dealing with optimal diagnostic as well as therapeutic approach. Congenital CMV infection is the most common vertically transmitted infection in developed countries. In 85–95% of newborns it runs asymptomatic, while in others it is presented with jaundice, petechias, hepatosplenomegaly and central nervous system damage. A1AT deficiency is on the other hand, the most common genetic liver disease in children, and the clinical spectrum varies from the accidentally detected increased levels of transaminases through to the severe infant cholestasis that can progress to cirrhosis. The following case report describes a two-month old male with severe clinical presentation of congenital CMV infection probably exacerbated due to A1AT deficiency comorbidity. The clinical manifestations and unusually difficult clinical signs this infant presented lead to assumption that the additional liver damage exists. Extensive laboratory analyses were performed, including PCR for CMV DNA, A1AT serum concentration, A1AT genotyping, followed and confirmed with phenotyping. Patient was treated parenteral with ganciclovir, what continued with oral valganciclovir and supportive therapy. Intensive and thorough supportive treatment of the infant resulted in satisfactory progress and excellent outcome. Patient was followed-up till the age of 18 months. The presented case provides excellent example about successful overcoming obstacles in differential diagnosis of A1AT in neonates and infants. Medical charts analysis was the methodology used in making this report.