[Epidemiology of allergic diseases]. / Epidemiologija alergijskih bolesti.

The article gives a critical review of the main epidemiological features of allergic diseases, their frequency, distribution and etiologic background as well as the possibilities of prevention and control, based on current literature. Statistical data for Croatia, collected by the Croatian National Institute of Public Health, are used to present actual epidemiological situation in Croatia. Basic descriptive epidemiological methods were used to express age and sex distribution, etc. In comments and review of preventive measures, our own epidemiological experiences and experience acquired on creating the national programs of health measures were used. The genesis of allergies usually implies the influence of various potent environmental allergens such as proteins or smaller molecules attached to proteins (haptens) through repeat or continuous exposure by contact, alimentary or respiratory route, and parenteral route as most efficient (mucous membrane exposure is similar to parenteral exposure). In addition, almost all substances from our environment may, under certain circumstances, become allergens and produce allergic reaction. Individual constitution that is inherited also plays a role. Allergic diseases are present all over the world, however, with variable frequency. Response to an allergen is generally the same, causing distinct allergic diseases like urticaria, anaphylactic shock, asthma, etc., while the main allergens can be different. It is estimated that 30%-40% of all people have some type or manifestation of allergy. According to our Institute data, in Croatia hospitalization was mostly required for allergic urticaria and allergic asthma, followed by Quincke's edema. Optimal treatment and appropriate healthcare structure are essential for efficient control and prevention of allergic diseases. The main direct elements are as follows: well organized emergency service for anaphylactic and other severe conditions; health education expected from all levels of healthcare system; allergology outpatient services available; and sufficient hospital capacities. An indirect yet important element is optimal drug prescribing and usage practice. Other specific public health measures include: pollen air concentration monitoring by public health institutes; information on particular allergen presence and intensity via public media; and control of potential allergen emission into the environment, especially air. People will, as always, find ways to adapt themselves and cope with allergies, with medical profession helping them by identifying the reasons causing allergic diseases and developing successful measures of treatment, prevention and control.

[Virologic and epidemiological characteristics of non-polio infection in Croatia over a ten-year period (2000-2009)]. / Non-polio enterovirusne infekcije u Hrvatskoj tijekom desetogodisnjeg razdoblja (2000.-2009.): viroloske i epidemioloske znacajke.

AIM: The aim of the present study was to show the virologic and epidemiological characteristics of non-polio enterovirus (NPEV) infection over a ten-year period in Croatia. METHODS: During the 2000-2009 period, the Laboratory for Enteroviruses, Croatian Public Health Institute analyzed 2754 clinical samples collected from 1880 patients with a clinical picture of enteroviral infection. The diagnosis of enteroviral infection was confirmed by virus isolation in cell culture. Viruses were typed using indirect immunofluorescence and/or neutralization assay. RESULTS: NPEV was proven in 394 (21%) of 1880 patients. Males were more commonly infected than females, at a ratio of 1.8:1, while the number of infected cases was highest among preschoolers and schoolchildren. Patients with isolated NPEV were most frequently diagnosed with aseptic meningitis (234/394; 59.4%). Infections were most commonly caused by echoviruses (218/394; 55.3%), followed by Coxsackie B (126/394; 32.0%) and Coxsackie A (31/394; 7.9%) viruses, rarely by echovirus 22 - parechovirus 1 (16/394; 4.1%) and enterovirus 71 (3/394; 0.8%). In most cases, echoviruses of the following serotypes were proven: 6, 9, 11, 13, 14, 18 and 30 (45/218, 21%; 14/218, 6.4%; 18/218, 8.3%; 15/218, 6.9%; 11/218, 5.0%; 55/218, 25.2% and 42/218, 19.3%), while serotypes 2, 3, 4, 5, 7, 12, 20, 21,25 and 26 were evidenced in a minority of patients or individual cases. Coxsackie B5 was the predominant serotype among Coxsackie B viruses (50/126, 40%), while Coxsackie A9 was most common Coxsackie A virus (26/31, 84%). Coxsackie B5 and B4 viruses were continually detected during the study period and appeared more frequently every four to five years. The most common echovirus isolate was echovirus 18, detected continually between 2000 and the outbreak year of 2006. Echovirus 6 and echovirus 30 were also isolated continually with peaks in 2002 and 2008, or 2002, 2006 and 2008. CONCLUSION: The results of this study pointed to a specific pattern of the occurrence of certain NPEV serotypes in Croatia. The epidemic pattern (echovirus 18 and Coxsackie 81) was characterized by peaks with an elevated number of isolations in given years. Contrary to this, endemic viruses were isolated in similar counts every year (Coxsackie B3), or manifested milder epidemic peaks every few years (echoviruses 30 and 6, Coxsackie B4 and B5). Data on NPEV infections, given their serotype and specific pattern of occurrence, contribute significantly to prompt diagnostic, clinical and epidemiological response to NPEV infections.

Clinical and molecular characterization of a parechovirus type 1 outbreak in neonates in Croatia.

During July 2009 an outbreak in neonates represented with gastrointestinal and respiratory symptoms was observed at the Neonatal Postintensive Care Unit, Clinical Hospital Center, Zagreb. Human parechovirus type 1 (HPeV1) was isolated from seven patients, one of whom was asymptomatic. All but one were premature neonates with serious underlying conditions, and all recovered fully after several days. In order to characterize the HPeV1s, sequencing of the VP1/2A region was conducted on six isolates from the outbreak and four isolates detected in Croatia in 2008 and 2007. The analysis of sequence similarity showed that the nucleotide identity between the prototype strain (Harris) and HPeV1 isolated in Croatia was 76.5-77.5%. Croatian strains from 2007 and 2009 clustered together with strains from the Netherlands and Germany detected in 2003 and 2006, respectively, while strains from 2008 clustered with the strain from Finland detected in 2000. Change of the dominant strains each year may suggest antigenic variation as a result of viral response to specific immunity of the target population.

[Guidelines for prevention, control and treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA)]. / Smjernice za prevenciju, kontrolu i lijecenje infekcija koje uzrokuje meticilin-rezistentni Staphylococcus aureus (MRSA).

Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen throughout the world, and in Croatia as well. Therefore it was decided to develop guidelines with the aim to reduce the number of patients infected/colonized with MRSA in healthcare facilities and in nursing homes in Croatia, consequently reducing MRSA-related morbidity and mortality. An interdisciplinary team of experts developed these guidelines using existing international guidelines from different countries, and literature reviews about prevention, control, treatment and laboratory diagnosis of MRSA infections. Grades of evidence for specific recommendations were determined using CDC/HICPAC grading system. Categorization is based on existing data, theoretical basis, applicability and economic impact. After a broad discussion in different professional societies, Guidelines were accepted. Guidelines include recommendations for measures in prevention of MRSA spread, role of hospital management, rational use of antibiotics, measures in a case of outbreak, treatment of infections and brief review of community-acquired MRSA. At the end, appendices concerning hospital audit, algorithms of laboratory diagnosis, patient information and form for national MRSA surveillance were added.

Vaccine regulations in Croatia.

In this paper legal prerequisites for vaccine licensure in Croatia are discussed. The Croatian legislation concerning vaccine licensing, marketing authorisation and utilization is reviewed. The procedures for including a vaccine into the Mandatory Childhood Vaccination Programme are also discussed with focus on Human papillomavirus (HPV) vaccines. Non-obligatory vaccination recommendations are given when according to professional opinion; vaccination is beneficial for the vaccinee. There is little doubt that HPV vaccines should be recommended for preadolescent girls in Croatia. However, reaching a decision on its possible introduction into the Childhood Vaccination Programme will require careful consideration of the larger picture and a comparison of the cost-effectiveness of a mandatory vaccination against other competing public health priorities.

[Epidemiologic characteristic of hepatitis B in the Splitsko-Dalmatinska County]. / Epidemioloske karakteristike hepatitisa B u Splitsko-Dalmatinskoj zupaniji.

Epidemiologic characteristics of hepatitis B virus (HBV) infection in the Split-Dalmatia County and in Croatia as a whole from January 1, 1994 till December 31, 2003 were analyzed. The mean number of hepatitis B cases was 28 (morbidity rate 6.03 per thousand) in the Split-Dalmatia County and 208 (morbidity rate 4.68 per thousand) in Croatia. Over the last five years, there was a marked decrease in the incidence of hepatits B in the Split-Dalmatia County (morbidity rate 1.55 per thousand), whereas its incidence at the national level showed a stable pattern (morbidity rate 4.49 per thousand). In the Split-Dalmatia County, the majority of patients (57.51%) were aged 15-29, which could be attributed to risky sexual contacts and intravenous drug use. The male to female ratio was 2.1(188:93). There was no major incidence fluctuation according to months of year. The hepatitis B mortality rate was 0.24% (5/2079) in Croatia as a whole, whereas no case of HBV lethality was recorded in the Split-Dalmatia County. The significant decrease in the hepatitis B morbidity rate in the Split-Dalmatia County most probably resulted from the comprehensive measures of prevention, especially vaccination, the early introduction of the needle exchange program (1955-1996).

[The biggest epidemic of hemorrhagic fever with renal syndrome in Croatia]. / Najveca epidemija hemoragijske vrucice s bubreznim sindromom u Hrvatskoj.

INTRODUCTION: The largest outbreak of hemorrhagic fever with renal syndrome (HFRS) to date occurred in Croatia in the year 2002. The epidemic started in winter, lasted throughout spring to summer months, ending not earlier than November. AIM: The aim of this study was to investigate and analyze the basic epidemiologic and clinical features of HFRS in Croatia by uniform and standardized prospective-retrospective analysis of all patients affected by the epidemic. PATIENTS AND METHODS: When the epidemic started, a patient questionnaire with questions on the basic demographic data, site of infection and other epidemiologic characteristics, clinical symptoms, disease severity and laboratory results was designed. Data on 401 patient with a clinical diagnosis of HFRS were collected. The etiologic diagnosis of the disease was confirmed by ELISA, and in some patients by indirect immunofluorescence test (IFT). The results were analyzed using a descriptive statistical method. RESULTS: HFRS was clinically diagnosed in 401 patients from all over Croatia. A total of 320 (79.8%) cases were reported to the Epidemiology Service of the National Institute of Public Health. The majority of patients (n = 128) were registered in June. Males were three times more affected than females. Apart from its long duration, this epidemic was characteristic for the involvement of general population, with only a small number of the affected from the potential risk groups (forestry workers 28, soldiers 14, farmers 18). The epidemic spread almost throughout inland Coratia. At least 44 patients were infected in the Plitvice Lakes area, 32 in Slunj, 27 on Sljeme, 24 in Velika, and at least 19 in the area of Kutjevo. The youngest patient was aged 4 and the oldest 80 years. The majority of patients were treated in Zagreb (University Hospital for Infectious Diseases--110, Zagreb University Hospital Center--3), followed by Karlovac (71 inpatients and 39 outpatients), Pozega (n = 79), and Rijeka (n = 37). Serologic analysis (ELISA method) detected Puumala virus in 161 and Dobrava virus in only 17 patients. The disease was confirmed by immunofluorescence method in 53 patients (mostly in Kariovac). During the 2002 outbreak, HFRS clinically manifested mostly in a milder form with general symptoms and transitory renal insufficiency, while hemorrhages were rarely recorded. According to our disease severity score, a mild form of the disease was recorded in 65%, moderately severe in 28%, severe in 5% and extremely severe form in 2% of the patients. One patient died. Two thirds of the patients were hospitalized during the febrile stage of the disease. All patients had fever, whereas headache and pain in the lumbar region were recorded in more than 90% of cases, polyuria in 75%, oliguira and vomiting in approximately 50%, respiratory symptoms in 35%, and hemorrhages (mostly on the skin and mucous membranes), vision disturbances, conjunctivitis and diarrhea in approximately 25% of patients. ESR was elevated in 64% and CRP in 93% of patients. Leukocytosis was recorded in 25% and thrombocytopenia in 70% of patients. Increased values of urea and creatinine and signs of liver damage were recorded in approximately 50% of the patients. CONCLUSION: The largest outbreak of HFRS occurred in Croatia in 2002, with more than 400 diseased throughout Croatia. This epidemic confirmed our previous assumption that the whole Croatia, apart from its narrow coastline area and islands, is a natural focus of HFRS with different causative types of hantaviruses. Efforts should be made to conduct a comprehensive ecologic and mammologic study on hantaviruses and their biologic characteristics in these areas.