Outbreak of hand, foot and mouth disease caused by Coxsackie A16 virus in a childcare centre in Croatia, February to March 2011.

We describe an outbreak of hand, foot and mouth disease (HFMD) in a childcare centre in a district of Zagreb county, north-west Croatia. A total of eleven cases of HFMD occurred in the childcare centre and another nine were reported from nearby areas in the district. Coxsackie A16 virus was diagnosed in 13 clinical specimens obtained from 11 symptomatic and asymptomatic children. All cases resolved without complications.

Autochthonous dengue fever in Croatia, August-September 2010.

After information about a dengue case in Germany acquired in Croatia, health professionals and the public in Croatia were alerted to assess the situation and to enhance mosquito control, resulting in the diagnosis of a second case of autochthonous dengue fever in the same area and the detection of 15 persons with evidence of recent dengue infection. Mosquito control measures were introduced. The circumstances of dengue virus introduction to Croatia remain unresolved.

Spotlight on measles 2010: excretion of vaccine strain measles virus in urine and pharyngeal secretions of a child with vaccine associated febrile rash illness, Croatia, March 2010.

We describe excretion of measles vaccine strain Schwarz in a child who developed a febrile rash illness eight days after primary immunisation against measles, mumps and rubella. Throat swabs and urine specimens were collected on the fifth and sixth day of illness, respectively. Genotyping demonstrated measles vaccine strain Schwarz (genotype A). If measles and rubella were not under enhanced surveillance in Croatia, the case would have been either misreported as rubella or not recognised at all.

Transmission of the L-Zagreb mumps vaccine virus, Croatia, 2005-2008.

We report on three cases of symptomatic transmission of the L-Zagreb mumps vaccine virus from three vaccinated children to five adult contacts. The five contact cases were parents of the vaccinated children and presented with parotitis and in one case also with aseptic meningitis. The etiology of the contacts' illness was determined by viral culture, genomic sequencing, serology and epidemiological linking. Two of the vaccinated children developed vaccine associated parotitis as an adverse event three weeks following immunization. Symptoms in contact cases developed five to seven weeks after the vaccination of the children. The five contact cases, as well as the three children with adverse events recovered completely. The children had been vaccinated with MMR vaccine produced by the Institute of Immunology Zagreb, each of them with a different lot. One of the possible explanations for these adverse events is that the very low levels of wild mumps virus circulation in the last decade, combined with waning immunity in those who received one dose of vaccine or suffered from mumps in childhood, resulted in susceptible young adults and that this unique epidemiological situation allows us to detect horizontal transmission of mumps vaccine virus.

Role of epidemiologic information system in sudden death prevention among Croatia's haemodialysis patients.

The main aim of Croatia's epidemiological information system is to enable the monitoring of infectious diseases as well as to enable necessary interventions. Its 24-hour epidemiologic alert mechanism made it possible for initial reports of sudden death clusters in haemodialysis units to reach epidemiologists on the night of 12 October 2001. The alert about the sudden deaths among haemodialysis patients in two hospitals has prompted us to do an epidemiological inquiry during that night and early the next morning. It looked at suspicions of a possible link between Baxter Plivadial P-15 lot 2001F075 dialyser and these deaths. As the suspicion was based on a small amount of data, it needed confirmation from a countrywide inquiry involving the other 40 haemodialysis units. A phone inquiry showed that 23 haemodialysis deaths occurred on 8-13 October 2001. It suggested that also dialyser of a different type and lot (P-18 2001B17R) should be incriminated. During the inquiry (October 13), all haemodialysis units were informed of the suspicions regarding incriminated dialysers, and of the necessity of temporary withdrawal of these from use. The withdrawal on 13 October of incriminated dialysers stopped the deaths among haemodialysis patients. No more such sudden deaths have been recorded since that could be linked either to the described period or to this clinical picture.

Beta 2-microglobulin studies in endemic Balkan nephropathy.

The diagnosis of BEN and its differentiation from other chronic interstitial nephropathies are difficult because of the insidious onset as well as nonspecific morphological changes in the kidney. Early diagnosis of this disease is by clinical and laboratory findings which have not been universally accepted. This study was designed to determine if the frequency of increased urinary beta 2-microglobulin (U beta 2m) in village populations at risk to develop BEN was significantly higher than that seen in a control population. Individuals in the two population samples were classified in one of three categories: healthy, suspect or diseased. There were 23 individuals who met the criteria for the clinical diagnosis of BEN. Twenty (87%) of these had one or more positive tests for increased U beta 2m. The prevalence of kidney disease in the endemic village population sample was 13.4 times that for the control village population sample. The data show that the healthy individuals living in a village where BEN is endemic have 6.4 times greater chance of having tubular proteinuria than those living in a control area. The coincidence of the finding of U beta 2m in the urine of 87% of those sick with BEN and in 37 of the 342 (10.8%) people judged to be free of kidney disease suggests that a positive U beta 2m test is an early indicator of exposure to a nephrotoxic agent.

A fifteen year cohort based evaluation of beta 2-microglobulin as an early sign of Balkan endemic nephropathy.

The occurrence of elevated urinary beta 2-microglobulin (U beta 2m) has been established to be more common in village populations living in areas where BEN is endemic when compared to appropriate control population. In addition, beta 2-microglobulinuria is associated with BEN. It has been demonstrated that there is an increase in the U beta 2m in apparently healthy populations located in high risk areas. It is 15 years since the first systematic investigations of U beta 2m in the villages of Brod Posavina were conducted. The purpose of this study was to determine the value of a positive test for tubular proteinuria as defined by increased U beta 2m, in identifying individuals at risk to develop BEN. In these studies we followed two cohorts for 15 years: one group consisted of individuals who were positive for tubular proteinuria by U beta 2m testing in 1974; the second group was an age and sex matched group from the same village who were never positive after 12 testings in 1974. The results show that a positive test for U beta 2m is associated with 9.9 times greater relative risk of developing BEN when compared to controls that had no positive U beta 2m tests.

Relationship of anemia to Balkan endemic nephropathy.

Anemia has been reported to be an early sign of Balkan endemic nephropathy (BEN) occurring before the serum creatinine is elevated. This study was designed to determine if anemia occurred more frequently in an otherwise 'healthy' population living in an area where BEN is endemic when compared to a control population. Also, we wished to determine if any relationship existed between anemia and beta 2-microglobulinuria (beta 2mu) in these populations. The prevalence of anemia in the control village population was 7%, compared to 21.4% of the at-risk village population. These data suggest that anemia is a part of the pathophysiologic picture of endemic nephropathy, and that anemia can be found in an early, non-azotemic phase of the kidney disease.

[Hemorrhagic fever with renal syndrome in Croatia: incidence of infection in human and wild animal reservoirs]. / Hemoragijska groznica s bubreznim sindromom (HGBS) u Hrvatskoj: ucestalost infekcije u ljudi i divlji animalni rezervoari.

On the territory of Lika and Gorski Kotar a group of 300 forest workers and 260 persons from the general population were screened for Hantavirus antibodies (by the indirect immunofluorescence test). In the first group of examenees a mean of 1.6% were found positive, ranging from 0% (Gospic) to 3.2% (Ogulin). In the second groups a mean of 5.4% were positive, ranging from 4.4 to 8.9% (Delnice and Slunj, respectively). It is concluded that the Hantavirus infection rate in our natural foci of HFRS is higher than officially registered. Screening of micromammals for the presence of Hantavirus in their organs (lungs), using the direct immunofluorescence test, was undertaken on three locations: Planina Gornja (hillsides of the mountain Medvednica), a case of HFRS having been registered there previously, and Plitvicka Jezera and Velika Gorica (village of Kobilic) selected because of two previous epidemics of HFRS (1967 and 1989, respectively). On the first location, all 126 animals examined (10 different species) were Hantavirus negative. On the second location, 9 of the 165 animals examined (three species) were Hantavirus positive (5.4%), namely 6 bank voles (Clethrionomys glareolus) and three yellow-necked mice (Apodemus flavicollis). On the third location, where 141 animals was caught and examined (7 different species), 7 animals were positive (4.9%): 3 striped field mice (A. agrarius), 3 wood mice (A. sylvaticus) and 1 bank vole (Cl. glareolus). The findings suggest that in our natural foci of HFRS the circulation of the Hantavirus is sustained by several species of micromammals.

[Epidemiology of enteroviral meningitis in Croatia 1958-1988 with special emphasis on the great epidemic of 1988]. / Epidemiologija enterovirusnih meningitisa u Republici Hrvatskoj 1958-1988. s posebnim osvrtom na veliku epidemiju 1988. godine.

In 1988, there was a large outbreak of enteroviral meningitis in the Republic of Croatia and in other parts of Yugoslavia as well. A total of 4079 cases of enteroviral meningitis were registered with one fatal outcome (Mb 8.7 0/ooo). The outbreak was caused by echovirus 4. Analysis of epidemiological, virologic and ecological data for 1988, as well as for a number of previous years, showed the following: an upward morbidity trend observed from 1958 to 1979 turned to a high level stationary trend with irregular annual oscillations. A cyclic morbidity trend was noticed with peaks in 9-10 years. Seasonal peak was lower in July regularly. In 1988, age and sex distribution of the diseased persons differed from the usual picture, showing greater proportion of older age and women. The probable reason is in the long absence of echovirus 4 from the target population, resulting in low herd immunity. This caused greater proportion of older cases, among which women (mothers) had probably been more exposed to infections than men (nursing ill household members, laundry handling, etc). The epidemic years 1988 and 1979 were hot during spring and summer, at above-average level. Such climatic factors (high temperature) coupled with the sufficiently low level of herd immunity probably triggered in both examples the outbreak of enteroviral meningitis.

[An epidemic of legionnaires' disease in a hotel]. / Epidemija legionarske bolest u jednom hotelu.

An outbreak of legionnaires' disease and epidemic control measures taken at one of our hotels are described. Twenty (1% morbidity) hotel guests were affected with one dying. As a result of field investigations and survey the hot water supply system has been identified as the source of infection. Control measures which created conditions unfavourable to Legionella growth and replication in the hot water system stopped the outbreak.

[Reactivity and immunogenicity of Engerix B, the recombinant DNA vaccine against hepatitis B]. / Ispitivanje reaktogenosti i imunogenosti rekombinantne DNA vakcine protiv hepatitisa B "Engerix-B".

A group of 67 health workers with no markers indicating previous hepatitis B infection were vaccinated against hepatitis B with a new DNA recombinant vaccine, Engerix B (commercially manufactured by Smith-Kline-RIT, Belgium). Three injections were given according to the 0-1-6 schedule. One month after the last injection the vaccinees were tested for anti-HBs antibodies by the enzyme-linked assay. Antibody titers equal or less than 10 mIU/ml were found only in three subjects or in 4.5% of them. Titers ranging from 11 to 99 mIU/ml were found in 7 subjects (10.4%), from 100 to 999 mIU/ml in 28 (41.8%) and those equal or more than 1000 mIU/ml in 29 subjects (43.3%). It is inferred that the seroconversion rate is 95.5%. Only one subject did not develop detectable antibodies but three subjects had titers over 10000 mIU/ml. No one developed overt hepatitis B during the trial nor did the high responders experienced inapparent infections. They were tested for anti HBc with negative results. Postvaccinal reactions were mild and almost exclusively local. There were no complications. For its high immunogenicity and acceptable reactogenicity the Engerix B vaccine has a promising future.

Characteristics of proteinuria in endemic nephropathy.

Subjects living in the endemic area of Posavina round Slavonski Brod have a significantly greater incidence of proteinuria (13.6%) than those living under the same conditions in the area where endemic nephropathy has not been observed (5.5%). Following determination of the grade and type of proteinuria, physiologic proteinuria was found in 36% of subjects from the endemic area. In nonphysiologic proteinuria the incidence of tubular proteinuria was 41%. A slight selective glomerular proteinuria was found in 51%, and other types of proteinuria in 8% of subjects. Tubular proteinuria was significantly higher in the endemic area than in the control area. The subjects with tubular proteinuria from the endemic area excrete significantly greater amounts of beta 2-microglobulin and light immunoglobulin chains.

Small terrestrial mammals as reservoirs of leptospires in the Sava Valley (Croatia).

Small mammals trapped in seven sites along the river Sava in Croatia were examined for leptospiral infection by renoculture and serological methods. Of the 1749 animals caught 702 were examined by renoculture method and 626 were tested by microagglutination-lysis. The dominant animals species caught were Microtus arvalis (672 animals) and Apodemus agrarius (552 animals). Of the 115 strains of leptospires isolated the dominant serotypes were L. grippotyphosa (40) and L. pomona (35). Five strains of L. sejroe, 9 strains of L. australis, 1 strain of L. bataviae and 25 undetermined strains were isolated, the infection rate ranging from 3 to 32%. Serologic evidence of infection was demonstrated in 91 animals, the prevalence ranging from 0 to 43% of animals depending on the trapping site. Specific agglutinins most frequently encountered were those against L. pomona (50) and L. grippotyphosa (26), though agglutinins against L. jalna (5), L. bataviae (4), L. bratislava (3) etc., were also found. A high degree if association between L. grippotyphosa and the common vole as well as between L. pomona and the field mouse was found indicating that as far as these two types of leptospires are concerned the Sava valley may be considered as their vast natural focus. It was also concluded that wild small mammals in this region of Croatia may be a source of leptospiral infection for the local population as well as for outdoor-reared domestic animals (swine, bovine).