Epidemiology of Balkan endemic nephropathy.

The first outbreak of Balkan endemic nephropathy (BEN) was reported between 1955 and 1957, initially in Serbia and soon afterwards in Croatia and in Bosnia and Herzegovina. The disease appears to be of a focal nature. In Yugoslavia at least six foci are known, generally along major rivers of the Danubian river basin, in areas that have often been flooded in the past and even today suffer from high ground waters. The prevalence rate of the disease is reported to be between 2 and 10%. In the endemic area of Croatia, a systematic survey of 'in-the-field' cases of the disease since 1975 has shown a prevalence between 0.5 and 4.4%. When suspected cases are also included the prevalence rises to 20% or more. Specific mortality (based on official statistics) during the period 1957-1984 averaged 1.54/1000 per annum, but some studies have shown that mortality is actually more than twice as high as this figure. More women are affected than men; women also more frequently die of BEN than men. Lethality is extremely high. A striking feature of BEN is the familial occurrence of the disease. Incidence does not seem to be connected with ethnic group differences. Immigrants into the endemic area may also contract the disease. An increased incidence of malignant tumours of the urinary tract has been recorded in populations living in endemic areas. Epidemiological characteristics suggest that the disease is contracted in the domestic situation, or possibly from other family members. Factors to be considered are food, water or long close contact. It is also possible that the disease is contracted outside the house, in connection with farming activities, since the affected persons are almost exclusively farmers.

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.

Murine typhus on the northern Dalmatian islands, Yugoslavia.

The present epidemiological study had the objective to establish whether and to what extent resident islander populations might be affected by the natural foci of murine typhus. To this end, 294 serum specimens were collected during summer and autumn of 1985 from the northern Dalmatian islanders, all of which were tested for anti-Rickettsia typhi (R. typhi) complement fixing (CF) antibodies. These were detected and confirmed at both stages of the screening, namely during the first stage, conducted on the northern Dalmatian islands, where 63.3% of the representative population had a titre of 1:4 or higher and during the second stage, carried out on the island of Vir, with 68.1% of the residents found R. typhi positive unlike in the former. The majority of positive sera were found in the 21-60-year group, peaking in the 21-30- and 31-40-year groups with fewer positive sera among the subjects over 60 and the fewest among the residents below 20 years of life. Thus, current differences in antibody rates in various age groups were shown to be statistically significant. Murine typhus immunity in resident islander populations could be detected from the age of 10 years on, and was shown to become almost equal to the adult population's positive sera levels in the 16-20-year age group. No differences were revealed with regard to the infective agent exposure between the male and female populations representative of the total population or in any of the age groups.

An etiological approach to Balkan endemic nephropathy based on the investigation of two genetically different populations.

The direct inheritance as a possible etiologic factor of Balkan endemic nephropathy (BEN) has been studied in an endemic area in the district of Slavonski Brod (Croatia-Yugoslavia). The basis for the investigation was given by a natural experiment induced by immigration of people from Ukraina to the endemic and nonendemic areas near Slavonski Brod. 1,536 persons in endemic villages and 733 inhabitants from the villages, where BEN has not been found, were studied with the aim of establishing diagnosis or excluding BEN. The generally adopted criteria enabling to classify the examined persons into the following 3 groups have been used: (a) diseased of BEN; (b) suspect to be diseased of BEN, and (c) individuals without signs of a renal disease. In the endemic villages among the population of Croatian aborigines, 12,1% diseased and suspects have been revealed. Among the Ukrainian immigrants and their offsprings, 10.5% diseased and suspects have been found. The difference is not significant (t = 0.7, p greater than 0.05). On the other hand, in nonendemic villages there were no diseased nor suspect BEN patients among the indigenous people as well as among the Ukrainians. The inference is suggested that the factors of the direct inheritance do not play a decisive role in the etiopathogenesis of BEN.

Ecological features of the tularemia natural focus in central Posavina (Croatia).

A five-year ecological study of the largest tularemia natural focus in Croatia (Yugoslavia) has revealed that the focus is of a meadow-field type and that the common vole is the crucial member of the local tularemia pathobiocenosis. The occurrence of epizootics and of concomitant epidemics is associated with the bionomy of the latter which, in its turn, is strongly influenced by environmental factors. It was possible therefore to link tularemia outbreaks with special meteorological and hydrological conditions, i.e. with warm and dry spring-summer seasons and the Sava river floods. The proper understanding of the underlying ecological laws furnishes a sound basis for the forecasts of future epidemiological events.