Arne Svedmyr

Isolation and propagation of nephropathia epidemica virus in bank voles.

Three strains of nephropathia epidemica (NE) virus were isolated from lung tissues of bank voles (Clethrionomys glareolus) and a grey-sided vole (C. rufocanus) trapped in Västerbotten county, Sweden. Two of these isolates were serially passaged in seronegative laboratory-bred bank voles. Experimentally infected animals developed a subclinical infection characterized by virus persistence, particularly in lung tissue. Attempts to infect other species of colonized rodents with NE virus and to isolate NE virus from acute phase patient blood were unsuccessful. The serial propagation of NE virus in colonized bank voles provides opportunities to study experimental infection in its reservoir rodent host.

An Epidemic Among Swedish Children Caused by Adenovirus Type 3

An epidemic of “pharyngoconjunctival fever” which occurred in the middle of Sweden in the summer of 1955 is described. A correlation to infections with adenovirus type 3 was found.

A study of the association of Echo viruses to aseptic meningitis

During the fall of 1954 34 strains of ECHO-6 virus were isolated from a total of 130 Stockholm patients with aseptic meningitis. From other cases in this material a few strains of ECHO virus (types 5 and 7), poliovirus and Coxsackie virus were recovered in the tissue culture test. Among control cases with various diseases ECHO-6 virus was isolated in 4 cases only, two of which were family contacts of a patient with meningitis excreting ECHO-6 virus. Together with the corresponding serological findings in neutralization and CF tests these results suggest an etiological relationship of ECHO-6 virus to the syndrome of aseptic meningitis in those patients from whom this virus was isolated. This concept is further supported by the similar findings in other laboratories. The presence of CF antibodies against an antigen containing live ECHO-6 virus was noted in several virus-negative cases lacking appreciable amounts of ECHO-6 neutralizing antibodies. Moreover, a response to heat-inactivated poliovirus antigens, apparently heterotypic in nature, occurred in many of the patients infected with ECHO-6 virus. In the year of 1954 the frequency of poliomyelitis was low in contrast to 1953, when Stockholm had a severe epidemic of this disease. During the last-mentioned year many cases of aseptic meningitis also occurred. The majority of these were apparently caused by the predominant poliovirus. However, a small number of cases excreted ECHO viruses, mainly of type 9.

Varicella virus in HeLa cells.

A strain of varicella virus was isolated and easily maintained in HeLa cells. The infection could be passed with live cells only, practically all infectivity being destroyed by disruption of the cells with sonication or repeated freeze-thawing, even if precautions were taken to favour the infectivity of nucleic acids. Potent CF antigen was easily obtained from infected HeLa cultures. However, the high proportion of cross reactions in adult cases of herpes simplex hamper the diagnostic value of the CF test with varicella antigen.

On the occurrence of adenoviruses in Sweden.

I n the course of a study of some 800 stool specimens obtained in Stockholm during the epidemic of poliomyelitis in 1953 (21) five strains of adenoviruses were encountered. Similar agents were recovered from the stools of three patients with the diagnosis o€ mesenteric lymphadenitis. I n one of these cases the virus was also isolated from a mesenteric lymph node. The results of a detailed study of these first Swedish strains of adenoviruses have been reported previously (13). It was thus found that all strains shared complement fixing antigens with each other as well as with the agent RI-67 isolated by Hilleman & Werner (10) and with the Sutherland strain isolated by Neva & Enders (17). By neutralization tests on the other hand, the strains were separated into three groups. Other studies in the laboratory of Huebner (1 1) have established that these types of viruses can be classified together with agents isolated by them from various sources. The first report on such viruses thus seems to be that of Rowe and coworkers (19) on agents recovered from human adenoids. Various names for this virus group have been used by different authors, including APC (adenoidal-pharyngeal-conjunctival, (1 1) ), R I (respiratory illness, (10) ), and ARD (acute respiratory disease, ( 7 ) ) viruses. Recently the term Adenoviruses was agreed upon (5). Seventeen serologically distinct types of adenoviruses have so far been reported (18). By epidemiological, clinical and laboratory studies some types have, more or less definitely, been etiologically correlated to syndromes of human disease, such as various types of respiratory illnesses (10, 2, 7 , 3, 4) and kerato-conjunctivitis (12). The present paper is a report on the various strains of adenoviruses isolated in Sweden since 1953. Extensive data mll be given only in those cases where type 7 virus was isolated. The outbreaks of type 3 adenovirus

Rubella Immunity as Related to Age and History of Overt Disease

Serum specimens from 161 pregnant women or newborn children and from 280 females of different age groups, obtained in the cities of Stockholm and Eskilstuna, Sweden, were tested for neutralizing antibody to rubella virus, some of them also for hemagglutination-inhibiting antibody. Lack of NT antibody in undiluted serum suggested susceptibility to rubella in 15–20% of women of child-bearing age. There was some correlation — most evident in the younger age groups — between reported history of overt rubella and presence of NT antibody. The distribution of serum titers, NT as well as HI, and the actual rarity of reports on remote attacks of the disease suggested that ignorance of childhood rubella was the prime reason for the poorer correlation in adults.

The use of guinea pigs in tests for immunogenic capacity of poliomyelitis virus preparations.

The guinea pig, although apparently resistant to poliomyelitis virus infection, responds to inoculation of living or formol inactivated virus with the formation of neutralizing antibodies. The strenght of the reaction seems to be independent of whether the virus is active or not and, thus, correlated to the administered amount of antigen only. Determination of the minimal amount necessary to elicit antibody formation (extinction limit titration) seems to be a reliable method for assay of immunogenic capacity. Different strains of virus possess widely varying immunogenic capacities. The ratio of infectivity to extinction limit titer (immunogenic index) is an adequate measure of this quality. The importance of selecting for vaccine production Strains of great immunogenic capacity is emphasized.

Tick-borne meningoencephalomyelitis in Sweden.

Out of 176 patients, hospitalized in Stockholm during the summer and fall of 1956 for acute infections of the central nervous system, not less than 68 had antibodies against viruses of the Russian spring-summer/ louping ill group. During convalescence 30 of these cases showed a definite rise in antibody titer. The clinical picture was that described in Central European tick-borne encephalitis. Neutralizing antibodies were determined in cultures of Detroit-6 cells. Infected tissue culture fluid, inactivated withβ-propiolactone, was found suitable as complement-fixing antigen.

Electron microscopy of HeLa cells infected with agents of the adenovirus (APC-RI-ARD) group

As previously reported 1 patterns of regularly arranged particles appear in the nuclei of the host cells during the growth of a virus belonging to the adenovirus group (type 5 according to Huebners scheme3). Our finding s have recently been confirmed by Har/ord and co-workers 3 as well as by Morgan and collaborators 4. The study of the cellular changes and the occurrence of particles has been continued and related to the growth curve of the virus. Similar changes have in addition been obse~vefl after infection with a type 3 strain of the same virus group, i. e. the type used by Har/ord and Morgan.

Hospital Outbreak of Adenovirus Type 3 Infections

The clinical and virologic aspects of 38 infections with adenovirus type 3 are described. The material includes 9 patients, admitted directly to the hospital and 11 cases resulting from contact with them, as well as 18 nosocomial infections. A striking difference seems to exist between these groups with respect to the incidence and intensity of the clinical symptoms. The nosocomial outbreak was largely limited to one room, where the patients were systematically examined for virus and antibody occurrence with subsequent correlation to clinical symptoms. It seems possible to draw the following conclusions from the investigation, in contrast, to a certain extent, to those reached by other investigators: