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During the period of 1954-1986, 399 cases of haemorrhagic fever with renal syndrome (HFRS) were registered in Bulgaria with 63 (15.7%) deaths. Three hundred serum samples from 214 patients who had contracted the disease from 1957 to 1986 were investigated by indirect fluorescent antibody test (IF-AT). As antigen Vero-E6 cells infected with the Asian Hantaan virus were used, as well as lung sections from bank voles (Clethrionomys glareolus) infected with strains Udmurt and Kazan 6-Cg from the European part of the U.S.S.R. Specific antibodies were detected in 194 sera, i.e. in 90.6% of persons investigated: in 131 single serum samples and in 63 paired sera. The results of the serological studies which covered 53.6% of all known local cases showed the territorial distribution of the natural foci in this country and the aetiologic relationship with the HFRS virus from the European part of the U.S.S.R.

In 1975 in Bulgaria a severe epidemic of central nervous system (CNS) disease occurred. Clinically, histopathologically, and epidemiologically the cases resembled poliomyelitis, aseptic meningitis, meningoencephalitis, and, in some cases, encephalomyocarditis. About 21% of the 700 reported cases developed paralysis, 44 with fatal outcome [ref. 1]. In 65 cases, 92 strains of enterovirus of the same serologic type were isolated: 38 strains from the CNS, 10 from mesenteric lymph nodes and tonsils, and 44 from feces [ref. 1,2]. A typical representative strain, No. 258, isolated from the spinal cord of a 3-month-old baby who died on the 5th day of disease with signs of focal polioencephalitis, was selected for intensive study. Cross-neutralization tests established the antigenic identity of the Bulgarian 258 strain (Stanchev) with American strains of enterovirus type 71 (BrCr and JaFr strains) and Swedish strains of the same type (Nos. 52343, 52500, and 6041). From its biological [ref. 1,2], physicochemical [ref. 3], and antigenic properties, the etiological agent of this large epidemic can be classified as a member of enterovirus type 71, one of the most highly pathogenic of the recently recognized enteroviruses.

Virological and serological studies of an epidemic disease in Bulgaria, 1975, were carried out. Epidemiologically, clinically and pathomorphologically, the disease simulated almost all known forms of poliomyelitis, acute stem encephalitis, encephalomyocarditis and aseptic meningitis. The studies completely rules out the participation of polioviruses and provided comprehensive evidence for the etiological role of a peculiar enterovirus subsequently identified as enterovirus (EV) type 71 known in the literature since 1974. Altogether, in 1975 and 1976 from 65 cases of poliomyelitis-like disease (PLD) 92 strains of EV71 were isolated, including 37 strains from the brain and medulla, 1 from the cerebrospinal fluid, 10 from mesenterial lymph nodes and tonsils and 44 from faeces. In addition, in 282 convalescent cases of the disease, diagnostic seroconversion or high titers of antibody to this virus were demonstrated. The most successful virus isolation was achieved by inoculation of green monkey kidney cell cultures and newborn white mice. Bulgarian strains of enterovirus 71 regularly caused paralysis in monkeys and morphological poliomyelitis-like lesions in their CNS, and paralysis and myositis with Zenker necrosis in newborn white mice, cotton rats, Syrian hamsters, and 3-week-old cotton rats. The diseased rodents had much more virus in their mucles than in brains.

In May-September, 1975, an outbreak of epidemic disease clinically and pathomorphologically simulating nearly all known forms of poliomyelitis occurred predominantly among young infants in Bulgaria. Most cases presented benign aseptic meningitis, sometimes with a short period of general cerebra- symptoms. Paralytic forms, such as bulbar polioencephalitis, anterior poliomyelitis, isolated pareses of the facial nerve, occasional cases of encephalomyocarditis, etc., were observed in about 21% of all cases. Over one-fourth of the paralytic cases with bulbar symptoms ended fatally. In March, 1976 another sporadic fatal case of this disease was examined. No new cases occurred in 1977. Histopathological examinations in all fatal cases regularly revealed lesions in the grey matter of the medulla and spinal cord typical of acute anterior poliomyelitis and bulbar polioencephalitis, with some peculiar features of localization and depth of the involvement of the brain stem. The similarity to poliomyelitis and precariously rapid increase in the incidence led to the decision to urgently vaccinate the entire human population with Sabin's live poliovirus vaccine simultaneously in the whole country in order to produce interference with the circulating agent. This aim appeared to have been achieved partially because soon the number of new cases of the disease began to decrease; however, no sharp and complete break in the curve of the incidence occurred. By the time of mass vaccination, the results of virological examinations started before were not yet available. Later, comprehensive complete evidence was obtained that over 25 fatal and many other typical cases of the disease were associated with an enterovirus proved to be antigenically related to enterovirus 71. The diseases in Bulgaria, 1975, differ considerably in the frequency of paralytic forms and in severity from the epidemics caused by enterovirus 71 in Sweden, 1973, Australia, 1972--1973, USA, 1969--1972, and Japan, 1972--1973.